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Review

Mouse models for bacterial enteropathogen infections: insights into the role of colonization resistance

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Article: 2172667 | Received 02 Dec 2022, Accepted 18 Jan 2023, Published online: 16 Feb 2023

References

  • The burden of foodborne diseases in the WHO European Region. (WHO Regional Office for Europe, Copenhagen, Denmark, 2017).
  • CDC. Antibiotic resistance threats in the United States, 2019. (2019).
  • Organization, W. H. World health statistics 2021: monitoring health for the SDGs, sustainable development goals. (WHO, 2021).
  • ECDC), E. F. S. A. a. E. C. f. D. P. a. C. E. a. The European Union one health 2020 zoonoses report. EFSA Journal, doi:10.2903/j.efsa.2021.6971 (2021).
  • Mowat AM, Agace WW. Regional specialization within the intestinal immune system. Nat Rev Immunol. 2014;14(667–685). doi:10.1038/nri3738.
  • Torow N, Marsland BJ, Hornef MW, Gollwitzer ES. Neonatal mucosal immunology. Mucosal Immunol. 2017;10(5–17). doi:10.1038/mi.2016.81.
  • Schirmer M, Smeekens, S. P., Vlamakis, H., Jaeger, M., Oosting, M., Franzosa, E. A. & Xavier, R. J. Linking the human gut microbiome to inflammatory cytokine production capacity. Cell. 2016;167:1125–36. doi:10.1016/j.cell.2016.10.020.
  • Walter J, Ley R. The human gut microbiome: ecology and recent evolutionary changes. Annu Rev Microbiol. 2011;65(411–429). doi:10.1146/annurev-micro-090110-102830.
  • Rojas CA, Ramirez-Barahona S, Holekamp KE, Theis KR. Host phylogeny and host ecology structure the mammalian gut microbiota at different taxonomic scales. Anim Microbiome. 2021;3(33). doi:10.1186/s42523-021-00094-4.
  • Nguyen TL, Vieira-Silva S, Liston A, Raes J. How informative is the mouse for human gut microbiota research? Dis Model Mech. 2015;8(1):1–16. doi:10.1242/dmm.017400.
  • Rajilic-Stojanovic M, Heilig HG, Tims S, Zoetendal EG, de Vos WM. Long-term monitoring of the human intestinal microbiota composition. Environ Microbiol. 2012. doi:10.1111/1462-2920.12023.
  • Kirk MD, Pires, S. M., Black, R. E., Caipo, M., Crump, J. A., Devleesschauwer, B. & Angulo, F. J. World health organization estimates of the global and regional disease burden of 22 foodborne bacterial, protozoal, and viral diseases, 2010: a data synthesis. PLoS Med. 2015;12(e1001921). doi:10.1371/journal.pmed.1001921
  • Havelaar AH, Kirk, MD, Torgerson, PR, Gibb, HJ, Hald, T, Lake, RJ, Praet, N, Bellinger, DC, de Silva, NR, Gargouri, N, Speybroeck, N, Cawthorne, A, Mathers, C, Stein, C, Angulo, FJ, Devleesschauwer, B. Vol. 12 (Public Library of Science 2015). doi:10.1371/journal.pmed.1001923.
  • Abt MC, McKenney PT, Pamer EG. Clostridium difficile colitis: pathogenesis and host defence. Nat Rev Microbiol. 2016;14(609–620). doi:10.1038/nrmicro.2016.108.
  • Lim SC, Knight DR, Riley TV. Clostridium difficile and One health. Clin Microbiol Infect. 2020;26(857–863). doi:10.1016/j.cmi.2019.10.023.
  • Furter M, Sellin ME, Hansson GC, Hardt WD. Mucus architecture and near-surface swimming affect distinct salmonella typhimurium infection patterns along the murine intestinal tract. Cell Rep. 2019;27:2665–2678. doi:10.1016/j.celrep.2019.04.106.
  • Ermund A, Schutte A, Johansson ME, Gustafsson JK, Hansson GC. Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer’s patches. Am J Physiol Gastrointest Liver Physiol. 2013;305:G341–347. doi:10.1152/ajpgi.00046.2013.
  • Roager HM, Hansen, L., Bahl, M. I., Frandsen, H. L., Carvalho, V., Gøbel, R. J. & Licht, T. R. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nat Microbiol. 2016;1(16093). doi:10.1038/nmicrobiol.2016.93
  • Arnoldini M, Cremer J, Hwa T. Bacterial growth, flow, and mixing shape human gut microbiota density and composition. Gut Microbes. 2018;9(559–566). doi:10.1080/19490976.2018.1448741.
  • Han S, Lu, Y., Xie, J., Fei, Y., Zheng, G., Wang, Z. & Li, L. Probiotic gastrointestinal transit and colonization after oral administration: a long journey. Front Cell Infect Microbiol. 2021;11(609722). doi:10.3389/fcimb.2021.609722
  • Takiishi T, Fenero CIM, Camara NOS. Intestinal barrier and gut microbiota: shaping our immune responses throughout life. Tissue Barriers. 2017;5(e1373208). doi:10.1080/21688370.2017.1373208.
  • Ducarmon QR, Zwittink, R. D., Hornung, B. V. H., Van Schaik, W., Young, V. B., & Kuijper, E. J. Gut microbiota and colonization resistance against bacterial enteric infection. Microbiol Mol Biol Rev. 2019;83. doi:10.1128/MMBR.00007-19.
  • Kreuzer M, Hardt WD. How Food affects colonization resistance against enteropathogenic bacteria. Annu Rev Microbiol. 2020;74(787–813). doi:10.1146/annurev-micro-020420-013457.
  • Stecher B, Berry D, Loy A. Colonization resistance and microbial ecophysiology: using gnotobiotic mouse models and single-cell technology to explore the intestinal jungle. FEMS Microbiology Reviews. 2013. doi:10.1111/1574-6976.12024.
  • Chen C, Yang X, Shen X. Confirmed and potential roles of bacterial t6SSS in the intestinal ecosystem. Front Microbiol. 2019;10(1484). doi:10.3389/fmicb.2019.01484.
  • Heilbronner S, Krismer B, Brotz-Oesterhelt H, Peschel A. The microbiome-shaping roles of bacteriocins. Nat Rev Microbiol. 2021;19(726–739). doi:10.1038/s41579-021-00569-w.
  • Rogers AWL, Tsolis RM, Baumler AJ. Salmonella versus the Microbiome. Microbiol Mol Biol Rev. 2021:85. doi:10.1128/MMBR.00027-19.
  • Nguyen BD, Cuenca, M., Hartl, J., Gül, E., Bauer, R., Meile, S. & Hardt, W. D. Import of aspartate and malate by DcuABC drives H2/fumarate respiration to promote initial salmonella gut-lumen colonization in mice. Cell Host Microbe. 2020;27:922–936. doi:10.1016/j.chom.2020.04.013.
  • Celis AI, Relman DA. Competitors versus collaborators: micronutrient processing by pathogenic and commensal human-associated gut bacteria. Mol Cell. 2020;78(570–576). doi:10.1016/j.molcel.2020.03.032.
  • Liou MJ, Miller, B. M., Litvak, Y., Nguyen, H., Natwick, D. E., Savage, H. P. & Bäumler, A. J. Host cells subdivide nutrient niches into discrete biogeographical microhabitats for gut microbes. Cell Host Microbe. 2022;30:836–847. doi:10.1016/j.chom.2022.04.012.
  • Wittebole X, De Roock S, Opal SM. A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence. 2014;5(226–235). doi:10.4161/viru.25991.
  • Shkoporov AN, Clooney, A. G., Sutton, T. D., Ryan, F. J., Daly, K. M., Nolan, J. A. & Hill, C. The human gut virome is highly diverse, stable, and individual specific. Cell Host Microbe. 2019;26:527–541. doi:10.1016/j.chom.2019.09.009.
  • Zhou A, Yuan, Y., Yang, M., Huang, Y., Li, X., Li, S. & Tang, B. Crosstalk Between the gut microbiota and epithelial cells under physiological and infectious conditions. Frontiers in Cellular and Infection Microbiology. 2022;12:832672. doi:10.3389/fcimb.2022.832672 .
  • Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014;14(141–153). doi:10.1038/nri3608.
  • Maier L, et al. Granulocytes impose a tight bottleneck upon the gut luminal pathogen population during Salmonella typhimurium colitis. PLoS Pathog. 2014;10(e1004557). doi:10.1371/journal.ppat.1004557
  • Kaiser P, Diard M, Stecher B, Hardt W-D. The streptomycin mouse model for Salmonella diarrhea: functional analysis of the microbiota, the pathogen’s virulence factors, and the host’s mucosal immune response. Immunological Reviews. 2012;245:56–83. doi:10.1111/j.1600-065X.2011.01070.x.
  • Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu Rev Immunol. 2012;30(459–489). doi:10.1146/annurev-immunol-020711-074942.
  • Molloy MJ, Bouladoux, N., Hand, T. W., Koo, L. Y., Naik, S. & Belkaid, Y. Intraluminal containment of commensal outgrowth in the gut during infection-induced dysbiosis. Cell Host Microbe. 2013;14(318–328). doi:10.1016/j.chom.2013.08.003
  • Moor K, Diard, M., Sellin, M. E., Felmy, B., Wotzka, S. Y., Toska, A. & Slack, E. High-avidity IgA protects the intestine by enchaining growing bacteria. Nature. 2017;544(498–502). doi:10.1038/nature22058
  • Mantis NJ, Rol N, Secretory Iga’s CB. complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011;4(603–611). doi:10.1038/mi.2011.41.
  • Pike CM, Theriot CM. Mechanisms of colonization resistance against clostridioides difficile. The Journal of Infectious Diseases. 2020;223:S194–S200. doi:10.1093/infdis/jiaa408.
  • Mizrahi A, Bruxelle JF, Pechine S, Le Monnier A. Prospective evaluation of the adaptive immune response to SlpA in Clostridium difficile infection. Anaerobe. 2018;54(164–168). doi:10.1016/j.anaerobe.2018.09.008.
  • Nagao-Kitamoto H, Nagao-Kitamoto, H., Leslie, J. L., Kitamoto, S., Jin, C., Thomsson, K. A., Gillilland III, M. G. & Kamada, N. Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota. Nat Med. 2020;26(608–617). doi:10.1038/s41591-020-0764-0
  • Wotzka SY, Kreuzer, M., Maier, L., Arnoldini, M., Nguyen, B. D., Brachmann, A. O. & Hardt, W. D. Escherichia coli limits Salmonella Typhimurium infections after diet shifts and fat-mediated microbiota perturbation in mice. Nat Microbiol. 2019. doi:10.1038/s41564-019-0568-5.
  • Bohnhoff M, Drake BL, Miller CP. Effect of streptomycin on susceptibility of intestinal tract to experimental Salmonella infection. Proc Soc Exp Biol Med. 1954;86(132–137). doi:10.3181/00379727-86-21030.
  • Hugenholtz F, de Vos WM. Mouse models for human intestinal microbiota research: a critical evaluation. Cell Mol Life Sci. 2018;75(149–160). doi:10.1007/s00018-017-2693-8.
  • Besser JM. Salmonella epidemiology: a whirlwind of change. Food Microbiol. 2018;71(55–59). doi:10.1016/j.fm.2017.08.018.
  • Chai SJ, Gu W, O’Connor KA, Richardson LC, Tauxe RV. Incubation periods of enteric illnesses in foodborne outbreaks, United States, 1998-2013. Epidemiol Infect. 2019;147(e285). doi:10.1017/S0950268819001651.
  • Axelrad JE, Olén, O., Askling, J., Lebwohl, B., Khalili, H., Sachs, M. C., & Ludvigsson, J. F. Gastrointestinal infection increases odds of inflammatory bowel disease in a nationwide case-control study. Clin Gastroenterol Hepatol. 2019;17:1311–1322. doi:10.1016/j.cgh.2018.09.034.
  • Doorduyn Y, Van Den Brandhof WE, Van Duynhoven YT, Wannet WJ, Van Pelt W. Risk factors for Salmonella Enteritidis and Typhimurium (DT104 and non-DT104) infections in The Netherlands: predominant roles for raw eggs in Enteritidis and sandboxes in Typhimurium infections. Epidemiol Infect. 2006;134(617–626). doi:10.1017/S0950268805005406.
  • Pavia AT, Shipman, L. D., Wells, J. G., Puhr, N. D., Smith, J. D., McKinley, T. W., & Tauxe, R. V. Epidemiologic evidence that prior antimicrobial exposure decreases resistance to infection by antimicrobial-sensitive Salmonella. J Infect Dis. 1990;161(255–260). doi:10.1093/infdis/161.2.255
  • Barthel M, Hapfelmeier, S., Quintanilla-Martínez, L., Kremer, M., Rohde, M., Hogardt, M. & Hardt, W. D. Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun. 2003;71 2839–2858).
  • Bakkeren E, Gül, E., Huisman, J. S., Steiger, Y., Rocker, A., Hardt, W. D., & Diard, M. Impact of horizontal gene transfer on emergence and stability of cooperative virulence in Salmonella Typhimurium. Nat Commun. 2022;13(1939). doi:10.1038/s41467-022-29597-7
  • Bakkeren E, Huisman, J. S., Fattinger, S. A., Hausmann, A., Furter, M., Egli, A. & Hardt, W. D. Salmonella persisters promote the spread of antibiotic resistance plasmids in the gut. Nature. 2019;573(276–280). doi:10.1038/s41586-019-1521-8
  • Bakkeren E, Diard M, Hardt W-D-D. Evolutionary causes and consequences of bacterial antibiotic persistence. Nature Reviews. Microbiology. 2020;18:479–490. doi:10.1038/s41579-020-0378-z.
  • Stecher B, Robbiani, R., Walker, A. W., Westendorf, A. M., Barthel, M., Kremer, M. & Hardt, W. D. Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. PLoS Biol. 2007;5:2177–2189. doi:10.1371/journal.pbio.0050244.
  • Stecher B, Paesold, G., Barthel, M., Kremer, M., Jantsch, J., Stallmach, T. & Hardt, W. D. Chronic Salmonella enterica serovar Typhimurium-induced colitis and cholangitis in streptomycin-pretreated Nramp1+/+ mice. Infect Immun. 2006;74(5047–5057). doi:10.1128/IAI.00072-06
  • Stecher B, Chaffron, S., Käppeli, R., Hapfelmeier, S., Freedrich, S., Weber, T. C. & Hardt, W. D. Like will to like: abundances of closely related species can predict susceptibility to intestinal colonization by pathogenic and commensal bacteria. PLoS Pathog. 2010;6(e1000711). doi:10.1371/journal.ppat.1000711
  • Maier L, Vyas, R., Cordova, C. D., Lindsay, H., Schmidt, T. S. B., Brugiroux, S. & Hardt, W. D. Microbiota-derived hydrogen fuels Salmonella typhimurium invasion of the gut ecosystem. Cell Host Microbe. 2013;14(641–651). doi:10.1016/j.chom.2013.11.002
  • Brugiroux S, Beutler, M., Pfann, C., Garzetti, D., Ruscheweyh, H. J., Ring, D. & Stecher, B. Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium. Nat Microbiol. 2016;2(16215). doi:10.1038/nmicrobiol.2016.215
  • Garzetti D, Brugiroux, S., Bunk, B., Pukall, R., McCoy, K. D., Macpherson, A. J., & Stecher, B. High-quality whole-genome sequences of the oligo-mouse-microbiota bacterial community. Genome Announc. 2017;5. doi:10.1128/genomeA.00758-17.
  • Stecher B, Macpherson, A. J., Hapfelmeier, S., Kremer, M., Stallmach, T., & Hardt, W. D. Comparison of Salmonella enterica serovar Typhimurium colitis in germfree mice and mice pretreated with streptomycin. Infect Immun. 2005;73(3228–3241). doi:10.1128/IAI.73.6.3228-3241.2005
  • Chung H, Pamp, S. J., Hill, J. A., Surana, N. K., Edelman, S. M., Troy, E. B. & Kasper, D. L. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012;149(1578–1593). doi:10.1016/j.cell.2012.04.037
  • Macpherson AJ, Harris NL. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol. 2004;4(478–485). doi:10.1038/nri1373.
  • Smith K, McCoy KD, Macpherson AJ. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol. 2007;19(59–69). doi:10.1016/j.smim.2006.10.002.
  • Yoo W, Zieba, J. K., Foegeding, N. J., Torres, T. P., Shelton, C. D., Shealy, N. G. & Byndloss, M. X. High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide. Science. 2021;373(813–818). doi:10.1126/science.aba3683
  • Lee JY, Cevallos, S. A., Byndloss, M. X., Tiffany, C. R., Olsan, E. E., Butler, B. P. & Bäumler, A. J. High-fat diet and antibiotics cooperatively impair mitochondrial bioenergetics to trigger dysbiosis that exacerbates pre-inflammatory bowel disease. Cell Host Microbe. 2020;28:273–284. doi:10.1016/j.chom.2020.06.001.
  • Zhang K, Riba, A, Nietschke, M, Torow, N, Repnik, U, Pütz, A. Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo. PLoS Pathog. 2018;14:e1006925. doi:10.1371/journal.ppat.1006925.
  • Relman D ( Anand Jagatia ed) ( Nature Portfolio, 2019).
  • Maier L, Barthel, M, Stecher, B, Maier, RJ, Gunn, JS, et al. Salmonella Typhimurium strain ATCC14028 requires H2-hydrogenases for growth in the gut, but not at systemic sites. PLoS One. 2014;9(e110187). doi:10.1371/journal.pone.0110187
  • Stecher B, Barthel, M, Schlumberger, MC, Haberli, L, Rabsch, W, Kremer, M, Hardt, WD, et al. Motility allows S. Typhimurium to benefit from the mucosal defence. Cell Microbiol. 2008;10:1166–1180. doi:10.1111/j.1462-5822.2008.01118.x.
  • Stecher B, Hapfelmeier, S, Muller, C, Kremer, M, Stallmach, T, Hardt, WD, et al. Flagella and chemotaxis are required for efficient induction of Salmonella enterica serovar Typhimurium colitis in streptomycin-pretreated mice. Infect Immun. 2004;72(7):4138–50. doi:10.1128/IAI.72.7.4138-4150.2004
  • Hapfelmeier S, Ehrbar, K, Stecher, B, Barthel, M, Kremer, M, Hardt, WD, et al. Role of the Salmonella pathogenicity Island 1 effector proteins SipA, SopB, SopE, and SopE2 in Salmonella enterica subspecies 1 serovar Typhimurium colitis in streptomycin-pretreated mice. Infect Immun. 2004;72:795–809.
  • Hapfelmeier S, Stecher, B, Barthel, M, Kremer, M, Müller, AJ, Heikenwalder, M, Stallmach, T, Hensel, M, Pfeffer, K, Akira, S, Hardt, WD, et al. The Salmonella pathogenicity Island (SPI)-2 and SPI-1 type III secretion systems allow Salmonella serovar typhimurium to trigger colitis via MyD88-dependent and MyD88-independent mechanisms. J Immunol. 2005;174:16–1685.
  • Fattinger SA, Bock, D, Di Martino, ML, Deuring, S, Ventayol, PS, Ek, V, et al. Salmonella Typhimurium discreet-invasion of the murine gut absorptive epithelium. PLoS Pathog. 2020;16(e1008503). doi:10.1371/journal.ppat.1008503
  • Müller AJ, Kaiser, P, Dittmar, KE, Weber, TC, Haueter, S, Endt, K, et al. Salmonella gut invasion involves TTSS-2-dependent epithelial traversal, basolateral exit, and uptake by epithelium-sampling lamina propria phagocytes. Cell Host & Microbe. 2012;11(1):19–32.
  • Hausmann A, Felmy, B, Kunz, L, Kroon, S, Berthold, DL, Ganz, G, et al. Intercrypt sentinel macrophages tune antibacterial NF-kappaB responses in gut epithelial cells via TNF. J Exp Med. 2021;218:11. doi:10.1084/jem.20210862.
  • Litvak Y, Mon, KKZ, Nguyen, H, Chanthavixay, G, Liou, M, Velazquez, EM. Commensal Enterobacteriaceae protect against salmonella colonization through oxygen competition. Cell Host Microbe. 2019;25(1):128–139. doi:10.1016/j.chom.2018.12.003.
  • Rivera-Chavez F, Zhang, LF, Faber, F, Lopez, CA, Byndloss, MX, Olsan, EE, et al. Depletion of butyrate-producing clostridia from the gut microbiota drives an aerobic luminal expansion of salmonella. Cell Host Microbe. 2016;19(4):443–454. doi:10.1016/j.chom.2016.03.004
  • Winter SE, Thiennimitr, P, Winter, MG, Butler, BP, Huseby, DL, Crawford, RW. Gut inflammation provides a respiratory electron acceptor for Salmonella. Nature. 2010;467(7314):426–429.
  • Rivera-Chavez F, Lopez, CA, Zhang, LF, Cracia-Pastor, L, Chavez-Arroyo, A, Lokken, KL, Tsolis, RM, Winter, S, Bäumler, AJ, et al. Energy taxis toward host-derived nitrate supports a salmonella pathogenicity island 1-independent mechanism of invasion. mBio. 2016;7:4. doi:10.1128/mBio.00960-16.
  • Zaharik ML, Vallance BA, Puente JL, Gros P, Finlay BB. Host-pathogen interactions: host resistance factor Nramp1 up-regulates the expression of Salmonella pathogenicity Island-2 virulence genes. Proc Natl Acad Sci U S A. 2002;99(15705–15710). doi:10.1073/pnas.252415599.
  • Govoni G, Macrophage GP. NRAMP1 and its role in resistance to microbial infections. Inflamm Res. 1998;47(277–284). doi:10.1007/s000110050330.
  • Sellin ME, Muller, AA, Felmy, B, Dolowschiak, T, Diard, M, Tardivel, A, et al. Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa. Cell Host Microbe. 2014;16(2):237–248. doi:10.1016/j.chom.2014.07.001
  • Fattinger SA, Geiser, P, Samperio Ventayol, P, Di Martino, ML, Furter, M, Felmy, B, et al. Epithelium-autonomous NAIP/NLRC4 prevents TNF-driven inflammatory destruction of the gut epithelial barrier in Salmonella-infected mice. Mucosal Immunol. 2021;14(3):615–629. doi:10.1038/s41385-021-00381-y
  • Fattinger SA, Sellin ME, Hardt WD Vol. 59 86‐94 (Elsevier Ltd, 2021).
  • Hausmann A, Bock, D, Geiser, P, Berthold, DL, Fattinger, SA, Furter, M. Intestinal epithelial NAIP/NLRC4 restricts systemic dissemination of the adapted pathogen Salmonella Typhimurium due to site-specific bacterial PAMP expression. Mucosal Immunology. 2020;13(3)530–544. doi:10.1038/s41385-019-0247-0.
  • Hausmann A, Russo, G, Grossmann, J, Zünd, M, Schwank, G, Aebersold, R, et al. Germ-free and microbiota-associated mice yield small intestinal epithelial organoids with equivalent and robust transcriptome/proteome expression phenotypes. Cellular Microbiology. 2020;22(6):e13191. doi:10.1111/cmi.13191
  • Müller AA, Dolowschiak, T, Sellin, ME, Felmy, B, Verbree, C, Gadient, S, et al. An NK cell perforin response elicited via IL-18 controls mucosal inflammation kinetics during Salmonella gut infection. PLoS Pathogens. 2016;12(6):e1005723.
  • Songhet P, Barthel, M, Stecher, B, Müller, AJ, Kremer, M, Hansson, GC, et al. Stromal IFN-γR-signaling modulates goblet cell function during Salmonella Typhimurium infection. PloS one. 2011;6(7):e22459.
  • Agbor TA, Demma, Z, Mrsny, RJ, Castillo, A, Boll, EJ, McCormick, BA, et al. The oxido-reductase enzyme glutathione peroxidase 4 (GPX4) governs Salmonella Typhimurium-induced neutrophil transepithelial migration. Cell Microbiol. 2014;16(9):1339–1353. doi:10.1111/cmi.12290
  • Loetscher Y, Wieser, A, Lengefeld, J, Kaiser, P, Schubert, S, Heikenwalder, M, et al. Salmonella transiently reside in luminal neutrophils in the inflamed gut. PLoS One. 2012;7(4):e34812. doi:10.1371/journal.pone.0034812
  • Endt K, Stecher, B, Chaffron, S, Slack, E, Tchitchek, N, Benecke, A, et al. The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal salmonella diarrhea. PLoS Pathogens. 2010;6:9. doi:10.1371/journal.ppat.1001097.
  • Diard M, Bakkeren, E, Lentsch, V, Rocker, A, Bekele, NA, Hoces, D, et al. A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants. Nat Microbiol. 2021;6(7):830–841. doi:10.1038/s41564-021-00911-1
  • Salazar-Gonzalez RM, McSorley SJ. Salmonella flagellin, a microbial target of the innate and adaptive immune system. Immunol Lett. 2005;101:117–122. doi:10.1016/j.imlet.2005.05.004.
  • Sztein MB. Cell-mediated immunity and antibody responses elicited by attenuated Salmonella enterica Serovar Typhi strains used as live oral vaccines in humans. Clin Infect Dis. 2007;45(Suppl 1):S15–19. doi:10.1086/518140.
  • Murphy JR, Baqar, S, Munoz, C, Schlesinger, L, Ferreccio, C, Lindberg, AA, et al. Characteristics of humoral and cellular immunity to Salmonella typhi in residents of typhoid-endemic and typhoid-free regions. J Infect Dis. 1987;156(6):1005–1009. doi:10.1093/infdis/156.6.1005
  • Jacobson A, Lam L, Rajendram M, Tamburini F, Honeycutt J, Pham T, Van Treuren W, Pruss K, Stabler SR, Lugo K, et al. A gut commensal-produced metabolite mediates colonization resistance to salmonella infection. Cell Host Microbe. 2018;24(2):296–307. doi:10.1016/j.chom.2018.07.002.
  • Stecher B, Denzler, R, Maier, L, Bernet, F, Sanders, MJ, Pickard, DJ, et al. Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae PNAS. 2012; 109(4):1269–1274. doi:10.1073/pnas.1113246109.
  • Velazquez EM, Nguyen, H, Heasley, KT, Seachao, CH, Gil, LM, Rogers, AWL, et al. Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection. Nat Microbiol. 2019;4:1057–1064. doi:10.1038/s41564-019-0407-8.
  • Palmer JD, Mortzfeld, BM, Piattelli, E, Silby, MW, McCormick, BA, Bucci, V, et al. Microcin H47: a class IIb microcin with potent activity against multidrug resistant enterobacteriaceae. ACS Infect Dis. 2020;6(4):672–679. doi:10.1021/acsinfecdis.9b00302
  • Sassone-Corsi M, Nuccio, SP, Liu, H, Hernandez, D, Vu, CT, Takahashi, AA, et al. Microcins mediate competition among Enterobacteriaceae in the inflamed gut. Nature. 2016;540(7632): 280–283. doi:10.1038/nature20557
  • WHO. Campylobacter, https://www.who.int/news-room/fact-sheets/detail/campylobacter Accessed 4 November 2022. (2020).
  • Bereswill S, Fischer, A, Plickert, R, Haag, LM, Otto, B, Kühl, AA, Dasti, JI, et al. Novel murine infection models provide deep insights into the “menage a trois” of Campylobacter jejuni, microbiota and host innate immunity. PLoS One. 2011;6:e20953. doi:10.1371/journal.pone.0020953.
  • Heimesaat MM, Backert S, Alter T, Human Campylobacteriosis-A BS. Serious Infectious threat in a one health perspective. Curr Top Microbiol Immunol. 2021;431:51–23. doi:10.1007/978-3-030-65481-8_1.
  • Kaakoush NO, Castano-Rodriguez N, Mitchell HM, Man SM. Global epidemiology of campylobacter infection. Clin Microbiol Rev. 2015;28(687–720). doi:10.1128/CMR.00006-15.
  • Peterson MC. Clinical aspects of Campylobacter jejuni infections in adults. West J Med. 1994;161:148–152.
  • Mousavi S, Bereswill S, Heimesaat MM. Murine models for the investigation of colonization resistance and innate immune responses in campylobacter jejuni infections. Curr Top Microbiol Immunol. 2021;431(233–263). doi:10.1007/978-3-030-65481-8_9.
  • Gradel KO, Nielsen, HL, Schonheyder, HC, Ejlertsen, T, Kristensen, B, Nielsen, H, et al. Increased short- and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis. Gastroenterology. 2009;137 2 :495–501. doi:10.1053/j.gastro.2009.04.001
  • Peters S, Pascoe, B, Wu, Z, Bayliss, SC, Zeng, X, Edwinson, A, et al. Campylobacter jejuni genotypes are associated with post-infection irritable bowel syndrome in humans. Commun Biol. 2021;4:1015. doi:10.1038/s42003-021-02554-8
  • Mortensen NP, Kuijf, ML, Wim Ang, C, Schiellerup, P, Krogfelt, KA, Jacobs, BC, van Belkum, A, Ph Endtz, H, Bergman, MP, et al. Sialylation of Campylobacter jejuni lipo-oligosaccharides is associated with severe gastro-enteritis and reactive arthritis. Microbes Infect. 2009;11:12 988–994 . doi:10.1016/j.micinf.2009.07.004
  • Huizinga R, van den Berg, B, van Rijs, W, Tio-Gillen, A, Fokkink, WJR, Bakker-Jonges, LE, Geleijns, Karin, Samsom, JN, van Doorn, PA, Laman, JD, Jacobs, BC, et al. Innate immunity to campylobacter jejuni in guillain-barre syndrome. Ann Neurol. 2015;78(3): 343–354. doi:10.1002/ana.24442
  • Bucker R, Krug, SM, Moos, V, Bojarski, C, Schweiger, MR, Kerick, M, Fromm, A, et al. Campylobacter jejuni impairs sodium transport and epithelial barrier function via cytokine release in human colon. Mucosal Immunol. 2018;11(2):474–485. doi:10.1038/mi.2017.66
  • Mousavi S, Bereswill S, Heimesaat MM. Novel clinical campylobacter jejuni infection models based on sensitization of mice to lipooligosaccharide, a major bacterial factor triggering innate immune responses in human campylobacteriosis. Microorganisms. 2020:8. doi:10.3390/microorganisms8040482.
  • Chang C, Miller JF. Campylobacter jejuni colonization of mice with limited enteric flora. Infect Immun. 2006;74(5261–5271). doi:10.1128/IAI.01094-05.
  • Newell DG, Pearson A. The invasion of epithelial cell lines and the intestinal epithelium of infant mice by Campylobacter jejuni/coli. J Diarrhoeal Dis Res. 1984;2:19–26.
  • Newell DG, McBride H, Dolby JM. Investigations on the role of flagella in the colonization of infant mice with Campylobacter jejuni and attachment of Campylobacter jejuni to human epithelial cell lines. J Hyg (Lond). 1985;95(217–227). doi:10.1017/s0022172400062653.
  • Newell DG. Monoclonal antibodies directed against the flagella of Campylobacter jejuni: cross-reacting and serotypic specificity and potential use in diagnosis. J Hyg (Lond). 1986;96(377–384). doi:10.1017/s0022172400066134.
  • Haag LM, Fischer, A, Otto, B, Grundmann, U, Kühl, AA, Goebel, UB, Bereswill, S, Heimesaat, MM , et al. Campylobacter jejuni infection of infant mice: acute enterocolitis is followed by asymptomatic intestinal and extra-intestinal immune responses. Eur J Microbiol Immunol (Bp). 2012;2:2–11. doi:10.1556/EuJMI.2.2012.1.2
  • Haag LM, Fischer, A, Otto, B, Plickert, R, Kühl, AA, Goebel, UB, Bereswill, S, Heimesaat, MM, et al. Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice. PLoS One. 2012;7 5 :e35988. doi:10.1371/journal.pone.0035988
  • Ferreira RBR, Gill, N, Willing, BP, Antunes, LCM, Russell, SL, Croxen, MA, Finlay, BB, et al. The intestinal microbiota plays a role in Salmonella-induced colitis independent of pathogen colonization. PLoS One. 2011;6 5 :e20338. doi:10.1371/journal.pone.0020338
  • Russell SL, Gold, MJ, Hartmann, M, Willing, BP, Thorson, L, Wlodarska, M, Gill, N, et al. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep. 2012;13 5 :440–447. doi:10.1038/embor.2012.32
  • Stahl M, Ries, J, Vermeulen, J, Yang, H, Sham, HP, Crowley, SM, Badayeva, Y, et al. A novel mouse model of Campylobacter jejuni gastroenteritis reveals key pro-inflammatory and tissue protective roles for Toll-like receptor signaling during infection. PLoS Pathog. 2014;10 7 :e1004264. doi:10.1371/journal.ppat.1004264
  • Iizumi T, Taniguchi, T, Yamazaki, W, Vilmen, G, Alekseyenko, AV, Gao, Z, Perez, GIP, Blaser, MJ, et al. Effect of antibiotic pre-treatment and pathogen challenge on the intestinal microbiota in mice. Gut Pathog. 2016;8(60). doi:10.1186/s13099-016-0143-z
  • O’Loughlin JL, Samuelson, DR, Braundmeier-Fleming, AG, White, BA, Haldorson, GJ, Stone, JB, Lessmann, JJ, Eucker, Tyson, et al. The Intestinal microbiota influences campylobacter jejuni colonization and extraintestinal dissemination in mice. Appl Environ Microbiol. 2015;81 14 :4642–4650. doi:10.1128/AEM.00281-15
  • Stahl M, Vallance BA. Insights into Campylobacter jejuni colonization of the mammalian intestinal tract using a novel mouse model of infection. Gut Microbes. 2015;6(143–148). doi:10.1080/19490976.2015.1016691.
  • Mansfield LS, Bell, JA, Wilson, DL, Murphy, AJ, Elsheikha, HM, Rathinam, VAK, Fierro, BR, Linz, JE, Young, VB, et al. C57BL/6 and congenic interleukin-10-deficient mice can serve as models of Campylobacter jejuni colonization and enteritis. Infect Immun. 2007;75(3): 1099–1115. doi:10.1128/IAI.00833-06
  • Masanta WO, Heimesaat, MM, Bereswill, S, Tareen, AM, Lugert, R, Gross, U, Zautner, AE, et al. Modification of intestinal microbiota and its consequences for innate immune response in the pathogenesis of campylobacteriosis. Clin Dev Immunol. 2013;2013(526860). doi:10.1155/2013/526860
  • Heimesaat MM, Alutis, M, Grundmann, U, Fischer, A, Tegtmeyer, N, Boehm, M, Kühl, AA, Goebel, UB, Backert, S, Bereswill, S, et al. The role of serine protease HtrA in acute ulcerative enterocolitis and extra-intestinal immune responses during Campylobacter jejuni infection of gnotobiotic IL-10 deficient mice. Front Cell Infect Microbiol. 2014;4(77). doi:10.3389/fcimb.2014.00077
  • Heimesaat MM, Bereswill S. Murine infection models for the investigation of Campylobacter jejuni–host interactions and pathogenicity. Berl Munch Tierarztl Wochenschr. 2015;128(3–4):98–103.
  • Schmidt AM, Escher, U, Mousavi, S, Tegtmeyer, N, Boehm, M, Backert, S, Bereswill, S, Heimesaat, MM, et al. Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model. Gut Pathog. 2019;11(24). doi:10.1186/s13099-019-0306-9
  • Debruyne L, Gevers D, Vandamme P in Campylobacter 1-25 (2008).
  • Tegtmeyer N, Sharafutdinov, I, Harrer, A, Esmaeili, DS, Linz, B, Backert, S, et al. Campylobacter Virulence Factors and Molecular Host-Pathogen Interactions. Curr Top Microbiol Immunol. 2021;431: 169–202. doi:10.1007/978-3-030-65481-8_7
  • Li J, Gulbronson CJ, Bogacz M, Hendrixson DR, Thompson SA. FliW controls growth-phase expression of Campylobacter jejuni flagellar and non-flagellar proteins via the post-transcriptional regulator CsrA. Microbiology (Reading). 2018;164(1308–1319). doi:10.1099/mic.0.000704.
  • Ren F, Li, X, Tang, H, Jiang, Q, Yun, X, Fang, L, Huang, P, Tang, Y, Li, Q, Huang, J, Jiao, X, et al. Insights into the impact of flhF inactivation on Campylobacter jejuni colonization of chick and mice gut. BMC Microbiol. 2018;18(1):149. doi:10.1186/s12866-018-1318-1
  • Burnham PM, Hendrixson DR. Campylobacter jejuni: collective components promoting a successful enteric lifestyle. Nat Rev Microbiol. 2018;16(551–565). doi:10.1038/s41579-018-0037-9.
  • St Michael F, Szymanski, CM, Li, J, Chan, KH, Khieu, NH, Larocque, S, Wakarchuk, WW, Brisson, JR, Monteiro, MA, et al. The structures of the lipooligosaccharide and capsule polysaccharide of Campylobacter jejuni genome sequenced strain NCTC 11168. Eur J Biochem. 2002;269(21):5119–5136. doi:10.1046/j.1432-1033.2002.03201.x
  • Guerry P, Poly, F, Riddle, M, Maue, AC, Chen, Yu-Han, Monteiro, MA, et al. Campylobacter polysaccharide capsules: virulence and vaccines. Front Cell Infect Microbiol. 2012;2(7). doi:10.3389/fcimb.2012.00007
  • Rose A, Kay E, Wren BW, Dallman MJ. The Campylobacter jejuni NCTC11168 capsule prevents excessive cytokine production by dendritic cells. Med Microbiol Immunol. 2012;201(137–144). doi:10.1007/s00430-011-0214-1.
  • Kim S, Vela, A, Clohisey, SM, Athanasiadou, S, Kaiser, P, Stevens, MP, Vervelde, L, et al. Host-specific differences in the response of cultured macrophages to Campylobacter jejuni capsule and O-methyl phosphoramidate mutants. Vet Res. 2018;49(1):3. doi:10.1186/s13567-017-0501-y
  • Karlyshev AV, Ketley JM, Wren BW. The Campylobacter jejuni glycome. FEMS Microbiol Rev. 2005;29(377–390). doi:10.1016/j.femsre.2005.01.003.
  • Hameed A, Woodacre A, Machado LR, Marsden GL. An updated classification system and review of the lipooligosaccharide biosynthesis gene locus in campylobacter jejuni. Front Microbiol. 2020;11(677). doi:10.3389/fmicb.2020.00677.
  • Godschalk PC, Heikema, A. P., Gilbert, M., Komagamine, T. The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barre syndrome. J Clin Invest. 2004;114(1659–1665). doi:10.1172/JCI15707
  • Heimesaat MM, Lugert, R., Fischer, A., Alutis, M. Impact of Campylobacter jejuni cj0268c knockout mutation on intestinal colonization, translocation, and induction of immunopathology in gnotobiotic IL-10 deficient mice. PLoS One. 2014;9(e90148). doi:10.1371/journal.pone.0090148
  • Schmidt AM, Escher, U., Mousavi, S., Boehm, M. Protease activity of campylobacter jejuni HtrA modulates distinct intestinal and systemic immune responses in infected secondary abiotic IL-10 deficient mice. Front Cell Infect Microbiol. 2019;9(79). doi:10.3389/fcimb.2019.00079
  • Lobo de Sá FD, Butkevych, E., Nattramilarasu, P. K. Curcumin mitigates immune-induced epithelial barrier dysfunction by campylobacter jejuni. Int J Mol Sci. 2019;20(4830).
  • Mousavi S, Lobo de Sá, F. D., Schulzke, J. D., Bücker, R. Vitamin D in Acute campylobacteriosis-results from an intervention study applying a clinical campylobacter jejuni induced enterocolitis model. Front Immunol. 2019;10(2094). doi:10.3389/fimmu.2019.02094
  • Mousavi S, Escher, U., Thunhorst, E., Kittler, S. Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice. Sci Rep. 2020;10(2921). doi:10.1038/s41598-020-59890-8
  • Mousavi S, Schmidt, A. M., Escher, U., Kittler, S. Carvacrol ameliorates acute campylobacteriosis in a clinical murine infection model. Gut Pathog. 2020;12(2). doi:10.1186/s13099-019-0343-4
  • Mousavi S, Weschka D, Bereswill S, Heimesaat MM. Preclinical evaluation of oral urolithin-A for the treatment of acute campylobacteriosis in campylobacter jejuni infected microbiota-depleted IL-10(-/-) Mice. Pathogens. 2020:10. doi:10.3390/pathogens10010007.
  • Bereswill S, Mousavi S, Weschka D, Heimesaat MM. Disease-alleviating effects of peroral activated charcoal treatment in acute murine campylobacteriosis. Microorganisms. 2021:9. doi:10.3390/microorganisms9071424.
  • Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev. 1998;11(142–201). doi:10.1128/CMR.11.1.142.
  • Hartland EL, Leong JM. Enteropathogenic and enterohemorrhagic E. coli: ecology, pathogenesis, and evolution. Front Cell Infect Microbiol. 2013;3:15. doi:10.3389/fcimb.2013.00015.
  • Wales AD, Woodward MJ, Pearson GR. Attaching-effacing bacteria in animals. J Comp Pathol. 2005;132(1–26). doi:10.1016/j.jcpa.2004.09.005.
  • Moon HW, Whipp SC, Argenzio RA, Levine MM, Giannella RA. Attaching and effacing activities of rabbit and human enteropathogenic Escherichia coli in pig and rabbit intestines. Infect Immun. 1983;41(1340–1351). doi:10.1128/iai.41.3.1340-1351.1983.
  • Cantey JR, Blake RK. Diarrhea due to Escherichia coli in the rabbit: a novel mechanism. J Infect Dis. 1977;135(454–462). doi:10.1093/infdis/135.3.454.
  • Garcia A, Bosques, C. J., Wishnok, J. S., Feng, Y. Renal injury is a consistent finding in Dutch Belted rabbits experimentally infected with enterohemorrhagic Escherichia coli. J Infect Dis. 2006;193(1125–1134). doi:10.1086/501364
  • Sueyoshi M, Nakazawa M. Experimental infection of young chicks with attaching and effacing Escherichia coli. Infect Immun. 1994;62(4066–4071). doi:10.1128/iai.62.9.4066-4071.1994.
  • Tzipori S, Wachsmuth, I. K., Chapman, C., Birner, R., Brittingham, J., Jackson, C. The pathogenesis of hemorrhagic colitis caused by Escherichia coli O157: h7in gnotobiotic piglets. J Infect Dis. 1986;154(712–716). doi:10.1093/infdis/154.4.712
  • Gunzer F, Hennig-Pauka, I., Waldmann, K. H., Sandhoff, R. Gnotobiotic piglets develop thrombotic microangiopathy after oral infection with enterohemorrhagic Escherichia coli. Am J Clin Pathol. 2002;118(364–375). doi:10.1309/UMW9-D06Q-M94Q-JGH2
  • Dean-Nystrom EA, Stoffregen WC, Bosworth BT, Moon HW, Pohlenz JF. Early attachment sites for Shiga-toxigenic Escherichia coli O157: h7in experimentally inoculated weaned calves. Appl Environ Microbiol. 2008;74(6378–6384). doi:10.1128/AEM.00636-08.
  • Mohawk KL, O’Brien AD. Mouse models of Escherichia coli O157: h7infection and Shiga toxin injection. J Biomed Biotechnol. 2011;2011(258185). doi:10.1155/2011/258185.
  • Savkovic SD, Villanueva J, Turner JR, Matkowskyj KA, Hecht G. Mouse model of enteropathogenic Escherichia coli infection. Infect Immun. 2005;73(1161–1170). doi:10.1128/IAI.73.2.1161-1170.2005.
  • Dupont A, Sommer, F., Zhang, K., Repnik, U. Age-dependent susceptibility to enteropathogenic Escherichia coli (EPEC) infection in mice. PLoS Pathog. 2016;12(e1005616). doi:10.1371/journal.ppat.1005616
  • Ledwaba SE, Costa, D. V., Bolick, D. T., Giallourou, N. Enteropathogenic Escherichia coli infection induces diarrhea, intestinal damage, metabolic alterations, and increased intestinal permeability in a murine model. Front Cell Infect Microbiol. 2020;10(595266). doi:10.3389/fcimb.2020.595266
  • Wadolkowski EA, Burris JA, O’Brien AD. Mouse model for colonization and disease caused by enterohemorrhagic Escherichia coli O157:H7. Infect Immun. 1990;58(2438–2445). doi:10.1128/iai.58.8.2438-2445.1990.
  • Shimizu K, Asahara, T., Nomoto, K., Tanaka, R., Hamabata, T., Ozawa, A., & Takeda, Y. Development of a lethal Shiga toxin-producing Escherichia coli-infection mouse model using multiple mitomycin C treatment. Microb Pathog. 2003;35(1–9). doi:10.1016/s0882-4010(03)00065-2
  • Eaton KA, Friedman, D. I., Francis, G. J. Pathogenesis of renal disease due to enterohemorrhagic Escherichia coli in germ-free mice. Infect Immun. 2008;76(3054–3063). doi:10.1128/IAI.01626-07
  • Mohawk KL, Melton-Celsa AR, Zangari T, Carroll EE, O’Brien AD. Pathogenesis of Escherichia coli O157: h7strain 86-24 following oral infection of BALB/c mice with an intact commensal flora. Microb Pathog. 2010;48(131–142). doi:10.1016/j.micpath.2010.01.003.
  • Mundy R, Girard F, FitzGerald AJ, Frankel G. Comparison of colonization dynamics and pathology of mice infected with enteropathogenic Escherichia coli, enterohaemorrhagic E. coli and Citrobacter rodentium. FEMS Microbiol Lett. 2006;265:126–132. doi:10.1111/j.1574-6968.2006.00481.x.
  • Mullineaux-Sanders C, Suez J, Elinav E, Frankel G. Sieving through gut models of colonization resistance. Nat Microbiol. 2018;3(132–140). doi:10.1038/s41564-017-0095-1.
  • Luperchio SA, Schauer DB. Molecular pathogenesis of Citrobacter rodentium and transmissible murine colonic hyperplasia. Microbes Infect. 2001;3(333–340). doi:10.1016/s1286-4579(01)01387-9.
  • Petty NK, Bulgin, R., Crepin, V. F. The Citrobacter rodentium genome sequence reveals convergent evolution with human pathogenic Escherichia coli. J Bacteriol. 2010;192(525–538). doi:10.1128/JB.01144-09
  • Mullineaux-Sanders C, Sanchez-Garrido, J., Hopkins, E. G. Citrobacter rodentium-host-microbiota interactions: immunity, bioenergetics and metabolism. Nat Rev Microbiol. 2019;17(701–715). doi:10.1038/s41579-019-0252-z
  • McDaniel TK, Jarvis KG, Donnenberg MS, Kaper JB. A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. Proc Natl Acad Sci USA. 1995;92(1664–1668). doi:10.1073/pnas.92.5.1664.
  • McDaniel TK, Kaper JB. A cloned pathogenicity Island from enteropathogenic Escherichia coli confers the attaching and effacing phenotype on E. coli K-12. Mol Microbiol. 1997;23:399–407. doi:10.1046/j.1365-2958.1997.2311591.x.
  • Deng W, Li Y, Vallance BA, Finlay BB. Locus of enterocyte effacement from Citrobacter rodentium: sequence analysis and evidence for horizontal transfer among attaching and effacing pathogens. Infect Immun. 2001;69(6323–6335). doi:10.1128/IAI.69.10.6323-6335.2001.
  • Frankel G, Phillips, A. D., Novakova, M. Intimin from enteropathogenic Escherichia coli restores murine virulence to a Citrobacter rodentium eaeA mutant: induction of an immunoglobulin A response to intimin and EspB. Infect Immun. 1996;64(5315–5325). doi:10.1128/iai.64.12.5315-5325.1996
  • Higgins LM, Frankel, G., Connerton, I., Gonçalves, N. S. Role of bacterial intimin in colonic hyperplasia and inflammation. Science. 1999;285(588–591). doi:10.1126/science.285.5427.588
  • Frankel G, Phillips, A. D., Trabulsi, L. R. Intimin and the host cell–is it bound to end in Tir(s)? Trends Microbiol. 2001;9:214–218. doi:10.1016/s0966-842x(01)02016-9.
  • Deng W, Vallance BA, Li Y, Puente JL, Finlay BB. Citrobacter rodentium translocated intimin receptor (Tir) is an essential virulence factor needed for actin condensation, intestinal colonization and colonic hyperplasia in mice. Mol Microbiol. 2003;48(95–115). doi:10.1046/j.1365-2958.2003.03429.x.
  • Collins JW, Keeney, K. M., Crepin, V. F., Rathinam, V. A. Citrobacter rodentium: infection, inflammation and the microbiota. Nat Rev Microbiol. 2014;12(612–623). doi:10.1038/nrmicro3315
  • Silberger DJ, Zindl CL, Weaver CT. Citrobacter rodentium: a model enteropathogen for understanding the interplay of innate and adaptive components of type 3 immunity. Mucosal Immunol. 2017;10(1108–1117). doi:10.1038/mi.2017.47.
  • Geiger TL, Abt, M. C., Gasteiger, G. Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. J Exp Med. 2014;211(1723–1731). doi:10.1084/jem.20140212
  • Nordlander S, Pott J, Maloy KJ. NLRC4 expression in intestinal epithelial cells mediates protection against an enteric pathogen. Mucosal Immunol. 2014;7(775–785). doi:10.1038/mi.2013.95.
  • Hopkins EGD, Frankel G. Overview of the effect of citrobacter rodentium infection on host metabolism and the microbiota. Methods Mol Biol. 2021;2291(399–418). doi:10.1007/978-1-0716-1339-9_20.
  • Vallance BA, Deng W, Jacobson K, Finlay BB. Host susceptibility to the attaching and effacing bacterial pathogen Citrobacter rodentium. Infect Immun. 2003;71(3443–3453). doi:10.1128/IAI.71.6.3443-3453.2003.
  • Itoh K, Matsui T, Tsuji K, Mitsuoka T, Ueda K. Genetic control in the susceptibility of germfree inbred mice to infection by Escherichia coli O115a,c:K(B). Infect Immun. 1988;56(930–935). doi:10.1128/iai.56.4.930-935.1988.
  • Papapietro O, Teatero, S., Thanabalasuriar, A. R-spondin 2 signalling mediates susceptibility to fatal infectious diarrhoea. Nat Commun. 2013;4(1898). doi:10.1038/ncomms2816
  • Vaahtovuo J, Toivanen P, Eerola E. Bacterial composition of murine fecal microflora is indigenous and genetically guided. FEMS Microbiol Ecol. 2003;44(131–136). doi:10.1016/S0168-6496(02)00460-9.
  • Ghosh S, Dai, C., Brown, K., Rajendiran, E. Colonic microbiota alters host susceptibility to infectious colitis by modulating inflammation, redox status, and ion transporter gene expression. Am J Physiol Gastrointest Liver Physiol. 2011;301(G39–49). doi:10.1152/ajpgi.00509.2010
  • Willing BP, Vacharaksa A, Croxen M, Thanachayanont T, Finlay BB. Altering host resistance to infections through microbial transplantation. PLoS One. 2011;6(e26988). doi:10.1371/journal.pone.0026988.
  • Osbelt L, Thiemann, S., Smit, N., Lesker, T. R. Variations in microbiota composition of laboratory mice influence Citrobacter rodentium infection via variable short-chain fatty acid production. PLoS Pathog. 2020;16. e1008448. doi:10.1371/journal.ppat.1008448
  • Chen J, Waddell A, Lin YD, Cantorna MT. Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells. Mucosal Immunol. 2015;8(618–626). doi:10.1038/mi.2014.94.
  • Kamada N, Kim, Y. G., Sham, H. P., Vallance, B. A. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science. 2012;336(1325–1329). doi:10.1126/science.1222195
  • Kamada N, Sakamoto, K., Seo, S. U., Zeng, M. Y. Humoral immunity in the gut selectively targets phenotypically virulent attaching-and-effacing bacteria for intraluminal elimination. Cell Host Microbe. 2015;17(617–627). doi:10.1016/j.chom.2015.04.001
  • Kim YG, Sakamoto, K., Seo, S. U., Pickard, J. M. Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens. Science. 2017;356(315–319). doi:10.1126/science.aag2029
  • Mullineaux-Sanders C, Collins, J. W., Ruano-Gallego, D., Levy, M. Citrobacter rodentium Relies on commensals for colonization of the colonic mucosa. Cell Rep. 2017;21(3381–3389). doi:10.1016/j.celrep.2017.11.086
  • Herp S, Brugiroux, S., Garzetti, D., Ring, D. Mucispirillum schaedleri Antagonizes Salmonella Virulence to Protect Mice against Colitis. Cell Host Microbe. 2019;25:681–694. doi:10.1016/j.chom.2019.03.004.
  • Buschor S, Cuenca, M., Uster, S. S., Schären, O. P. Innate immunity restricts Citrobacter rodentium A/E pathogenesis initiation to an early window of opportunity. PLoS Pathog. 2017;13(e1006476). doi:10.1371/journal.ppat.1006476
  • Maattanen P, Lurz, E., Botts, S. R., Wu, R. Y., Yeung, C. W., Li, B. & Sherman, P. M. Ground flaxseed reverses protection of a reduced-fat diet against Citrobacter rodentium-induced colitis. Am J Physiol Gastrointest Liver Physiol. 2018;315:G788–G798. doi:10.1152/ajpgi.00101.2018.
  • Collins JW, Chervaux, C., Raymond, B., Derrien, M. Fermented dairy products modulate Citrobacter rodentium-induced colonic hyperplasia. J Infect Dis. 2014;210(1029–1041). doi:10.1093/infdis/jiu205
  • Desai MS, Seekatz, A. M., Koropatkin, N. M., Kamada, N. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167:1339–1353. doi:10.1016/j.cell.2016.10.043.
  • Zenewicz LA, Yin, X., Wang, G., Elinav, E. IL-22 deficiency alters colonic microbiota to be transmissible and colitogenic. J Immunol. 2013;190:5306–5312. doi:10.4049/jimmunol.1300016.
  • Varcoe JJ, Krejcarek G, Busta F, Brady L. Prophylactic feeding of Lactobacillus acidophilus NCFM to mice attenuates overt colonic hyperplasia. J Food Prot. 2003;66(457–465). doi:10.4315/0362-028x-66.3.457.
  • Johnson-Henry KC, Nadjafi, M., Avitzur, Y., Mitchell, D. J. Amelioration of the effects of Citrobacter rodentium infection in mice by pretreatment with probiotics. J Infect Dis. 2005;191(2106–2117). doi:10.1086/430318
  • Chen CC, Chiu CH, Lin TY, Shi HN, Walker WA. Effect of probiotics Lactobacillus acidophilus on Citrobacter rodentium colitis: the role of dendritic cells. Pediatr Res. 2009;65(169–175). doi:10.1203/PDR.0b013e31818d5a06.
  • Gareau MG, Wine E, Reardon C, Sherman PM. Probiotics prevent death caused by Citrobacter rodentium infection in neonatal mice. J Infect Dis. 2010;201(81–91). doi:10.1086/648614.
  • Rodrigues DM, Sousa AJ, Johnson-Henry KC, Sherman PM, Gareau MG. Probiotics are effective for the prevention and treatment of Citrobacter rodentium-induced colitis in mice. J Infect Dis. 2012;206(99–109). doi:10.1093/infdis/jis177.
  • Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003;52(827–833). doi:10.1136/gut.52.6.827.
  • Collins JW, Akin, A. R., Kosta, A., Zhang, N., Tangney, M., Francis, K. P., & Frankel, G. Pre-treatment with Bifidobacterium breve UCC2003 modulates Citrobacter rodentium-induced colonic inflammation and organ specificity. Microbiology (Reading). 2012;158(2826–2834). doi:10.1099/mic.0.060830-0
  • Fanning S, Hall, L. J., Cronin, M., Zomer, A., MacSharry, J., Goulding, D. & van Sinderen, D. Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection. Proc Natl Acad Sci USA. 2012;109(2108–2113). doi:10.1073/pnas.1115621109
  • Ivanov II, Atarashi, K., Manel, N., Brodie, E. L. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139(485–498). doi:10.1016/j.cell.2009.09.033
  • Woo V, Eshleman, E. M., Hashimoto-Hill, S., Whitt, J. Commensal segmented filamentous bacteria-derived retinoic acid primes host defense to intestinal infection. Cell Host Microbe. 2021;29:1744–1756. doi:10.1016/j.chom.2021.09.010.
  • Mullineaux-Sanders C, Carson, D., Hopkins, E. G., Glegola-Madejska, I. Citrobacter amalonaticus inhibits the growth of citrobacter rodentium in the gut lumen. mBio. 2021;12(e0241021). doi:10.1128/mBio.02410-21
  • Wu X, Vallance, B. A., Boyer, L., Bergstrom, K. S. Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on bacterial virulence factors. Am J Physiol Gastrointest Liver Physiol. 2008;294(G295–306). doi:10.1152/ajpgi.00173.2007
  • Curtis MM, Hu, Z., Klimko, C., Narayanan, S. The gut commensal Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape. Cell Host Microbe. 2014;16(759–769). doi:10.1016/j.chom.2014.11.005
  • Bergstrom KS, Kissoon-Singh, V., Gibson, D. L., Ma, C. Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa. PLoS Pathog. 2010;6(e1000902). doi:10.1371/journal.ppat.1000902
  • Lawson PA, Citron DM, Tyrrell KL, Finegold SM. Reclassification of clostridium difficile as clostridioides difficile (Hall and O’Toole 1935) Prevot 1938. Anaerobe. 2016;40(95–99). doi:10.1016/j.anaerobe.2016.06.008.
  • Bauer MP, et al. Clostridium difficile infection in Europe: a hospital-based survey. Lancet. 2011;377(63–73). doi:10.1016/S0140-6736(10)61266-4
  • Guh AY, Mu, Y., Winston, L. G., Johnston, H. Trends in U.S. Burden of clostridioides difficile infection and outcomes. N Engl J Med. 2020;382:1320–1330. doi:10.1056/NEJMoa1910215.
  • Kampouri E, Croxatto A, Prod’hom G, Guery B. Clostridioides difficile infection, still a long way to go. J Clin Med. 2021:10. doi:10.3390/jcm10030389.
  • Reigadas Ramirez E, Bouza ES. Economic burden of clostridium difficile infection in European Countries. Adv Exp Med Biol. 2018;1050(1–12). doi:10.1007/978-3-319-72799-8_1.
  • Fu Y, Luo Y, Grinspan AM. Epidemiology of community-acquired and recurrent Clostridioides difficile infection. Therap Adv Gastroenterol. 2021;14(17562848211016248). doi:10.1177/17562848211016248.
  • Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals. 207 (European Centre for Disease Prevention and Control, Stockholm, 2013).
  • Lessa FC, Mu, Y., Bamberg, W. M., Beldavs, Z. G. Burden of clostridium difficile infection in the United States. N Engl J Med. 2015;372(825–834). doi:10.1056/NEJMoa1408913
  • Penit A, Bemer, P., Besson, J., Cazet, L. Community-acquired Clostridium difficile infections. Med Mal Infect. 2016;46(131–139). doi:10.1016/j.medmal.2016.01.007
  • Warriner K, Xu C, Habash M, Sultan S, Weese SJ. Dissemination of Clostridium difficile in food and the environment: significant sources of C. difficile community-acquired infection? J Appl Microbiol. 2017;122:542–553. doi:10.1111/jam.13338.
  • Czepiel J, Dróżdż, M., Pituch, H., Kuijper, E. J. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis. 2019;38(1211–1221). doi:10.1007/s10096-019-03539-6
  • Crobach MJT, Vernon, J. J., Loo, V. G., Kong, L. Y. Understanding clostridium difficile colonization. Clin Microbiol Rev. 2018;31. doi:10.1128/CMR.00021-17.
  • Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2:16020. doi:10.1038/nrdp.2016.20.
  • Zacharioudakis IM, Zervou FN, Pliakos EE, Ziakas PD, Mylonakis E. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis. Am J Gastroenterol. 2015;110:381–390. doi:10.1038/ajg.2015.22.
  • Kuehne SA, Cartman, S. T., Heap, J. T., Kelly, M. L. The role of toxin A and toxin B in Clostridium difficile infection. Nature. 2010;467(711–713). doi:10.1038/nature09397
  • Chandrasekaran R, Lacy DB. The role of toxins in Clostridium difficile infection. FEMS Microbiol Rev. 2017;41(723–750). doi:10.1093/femsre/fux048.
  • Louie TJ, Miller, M. A., Mullane, K. M., Weiss, K., Lentnek, A., Golan, Y. & Shue, Y. K. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364(422–431). doi:10.1056/NEJMoa0910812
  • Johnson S, Louie, T. J., Gerding, D. N., Cornely, O. A., Chasan-Taber, S., Fitts, D. & Polymer Alternative for CDI Treatment (PACT) investigators. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014;59(345–354). doi:10.1093/cid/ciu313
  • Oksi J, Anttila VJ, Mattila E. Treatment of Clostridioides (Clostridium) difficile infection. Ann Med. 2020;52(12–20). doi:10.1080/07853890.2019.1701703.
  • Lee C, Louie, T. J., Weiss, K., Valiquette, L., Gerson, M., Arnott, W., & Gorbach, S. L. Fidaxomicin versus Vancomycin in the Treatment of Clostridium difficile Infection: Canadian Outcomes. Can J Infect Dis Med Microbiol. 2016;2016(8048757). doi:10.1155/2016/8048757
  • van Prehn J, Reigadas, E., Vogelzang, E. H., Bouza, E., Hristea, A., Guery, B. & Kuijper, E. J. European society of clinical microbiology and infectious diseases: 2021 update on the treatment guidance document for clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27(Suppl 2):S1–S21. doi:10.1016/j.cmi.2021.09.038.
  • Fekety R, Silva, J., Toshniwal, R., Allo, M., Armstrong, J., Browne, R. & Rifkin, G. Antibiotic-associated colitis: effects of antibiotics on Clostridium difficile and the disease in hamsters. Rev Infect Dis. 1979;1(386–397). doi:10.1093/clinids/1.2.386
  • Knoop FC. Clindamycin-associated enterocolitis in Guinea pigs: evidence for a bacterial toxin. Infect Immun. 1979;23(31–33). doi:10.1128/iai.23.1.31-33.1979.
  • Onderdonk AB, Cisneros RL, Bartlett JG. Clostridium difficile in gnotobiotic mice. Infect Immun. 1980;28(277–282). doi:10.1128/iai.28.1.277-282.1980.
  • Czuprynski CJ, Johnson WJ, Balish E, Wilkins T. Pseudomembranous colitis in Clostridium difficile-monoassociated rats. Infect Immun. 1983;39(1368–1376). doi:10.1128/iai.39.3.1368-1376.1983.
  • Chen X, Katchar, K., Goldsmith, J. D., Nanthakumar, N., Cheknis, A., Gerding, D. N., & Kelly, C. P. A mouse model of Clostridium difficile-associated disease. Gastroenterology. 2008;135(1984–1992). doi:10.1053/j.gastro.2008.09.002
  • Castro-Cordova P, Diaz-Yanez F, Munoz-Miralles J, Gil F, Paredes-Sabja D. Effect of antibiotic to induce Clostridioides difficile-susceptibility and infectious strain in a mouse model of Clostridioides difficile infection and recurrence. Anaerobe. 2020;62(102149). doi:10.1016/j.anaerobe.2020.102149.
  • Winston JA, Thanissery R, Montgomery SA, Theriot CM. Cefoperazone-treated mouse model of clinically-relevant clostridium difficile strain R20291. J Vis Exp. 2016. doi:10.3791/54850.
  • Studer N, Desharnais, L., Beutler, M., Brugiroux, S., Terrazos, M. A., Menin, L. & Hapfelmeier, S. Functional intestinal bile acid 7alpha-dehydroxylation by clostridium scindens associated with protection from clostridium difficile infection in a gnotobiotic mouse model. Front Cell Infect Microbiol. 2016;6(191). doi:10.3389/fcimb.2016.00191
  • Yamaguchi T, Konishi, H., Aoki, K., Ishii, Y., Chono, K., & Tateda, K. The gut microbiome diversity of Clostridioides difficile-inoculated mice treated with vancomycin and fidaxomicin. J Infect Chemother. 2020;26(483–491). doi:10.1016/j.jiac.2019.12.020
  • Lai YH, Tsai, B. Y., Hsu, C. Y., Chen, Y. H., Chou, P. H., Chen, Y. L. & Hung, Y. P. The role of toll-like receptor-2 in clostridioides difficile infection: evidence from a mouse model and clinical patients. Front Immunol. 2021;12(691039). doi:10.3389/fimmu.2021.691039
  • Pruss KM, Sonnenburg JL. C. difficile exploits a host metabolite produced during toxin-mediated disease. Nature. 2021;593:261–265. doi:10.1038/s41586-021-03502-6.
  • Deakin LJ, Clare, S., Fagan, R. P., Dawson, L. F., Pickard, D. J., West, M. R. & Lawley, T. D. The Clostridium difficile spo0A gene is a persistence and transmission factor. Infect Immun. 2012;80(2704–2711). doi:10.1128/IAI.00147-12
  • Jenior ML, Leslie JL, Young VB, Schloss PD. Clostridium difficile colonizes alternative nutrient niches during infection across distinct murine gut microbiomes. mSystems. 2017:2. doi:10.1128/mSystems.00063-17.
  • Jenior ML, Leslie JL, Young VB, Schloss PD. Clostridium difficile Alters the structure and metabolism of distinct cecal microbiomes during initial infection to promote sustained colonization. mSphere. 2018:3. doi:10.1128/mSphere.00261-18.
  • Koenigsknecht MJ, Theriot, C. M., Bergin, I. L., Schumacher, C. A., Schloss, P. D., & Young, V. B. Dynamics and establishment of Clostridium difficile infection in the murine gastrointestinal tract. Infect Immun. 2015;83(934–941). doi:10.1128/IAI.02768-14
  • Corthier G, Muller MC, Elmer GW, Lucas F, Dubos-Ramare F. Interrelationships between digestive proteolytic activities and production and quantitation of toxins in pseudomembranous colitis induced by Clostridium difficile in gnotobiotic mice. Infect Immun. 1989;57(3922–3927). doi:10.1128/iai.57.12.3922-3927.1989.
  • Aguirre AM, Yalcinkaya, N., Wu, Q., Swennes, A., Tessier, M. E., Roberts, P. & Sorg, J. A. Bile acid-independent protection against Clostridioides difficile infection. PLoS Pathog. 2021;17(e1010015). doi:10.1371/journal.ppat.1010015
  • Girinathan BP, DiBenedetto, N., Worley, J. N., Peltier, J., Arrieta-Ortiz, M. L., Immanuel, S. R. C. & Bry, L. In vivo commensal control of Clostridioides difficile virulence. Cell Host Microbe. 2021;29:1693–1708. doi:10.1016/j.chom.2021.09.007.
  • Corthier G, Muller MC, Wilkins TD, Lyerly D, L’Haridon R. Protection against experimental pseudomembranous colitis in gnotobiotic mice by use of monoclonal antibodies against Clostridium difficile toxin A. Infect Immun. 1991;59(1192–1195). doi:10.1128/iai.59.3.1192-1195.1991.
  • Bouillaut L, Self WT, Sonenshein AL. Proline-dependent regulation of Clostridium difficile Stickland metabolism. J Bacteriol. 2013;195(844–854). doi:10.1128/JB.01492-12.
  • Lopez CA, McNeely TP, Nurmakova K, Beavers WN, Skaar EP. Clostridioides difficile proline fermentation in response to commensal clostridia. Anaerobe. 2020;63(102210). doi:10.1016/j.anaerobe.2020.102210.
  • Ng KM, Ferreyra, J. A., Higginbottom, S. K., Lynch, J. B., Kashyap, P. C., Gopinath, S. & Sonnenburg, J. L. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature. 2013;502:96–99. doi:10.1038/nature12503.
  • Buffie CG, Bucci, V., Stein, R. R., McKenney, P. T., Ling, L., Gobourne, A. & Pamer, E. G. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2015;517(205–208). doi:10.1038/nature13828
  • Kang JD, Myers, C. J., Harris, S. C., Kakiyama, G., Lee, I. K., Yun, B. S. & Hylemon, P. B. Bile acid 7alpha-dehydroxylating gut bacteria secrete antibiotics that inhibit clostridium difficile: role of secondary bile acids. Cell Chem Biol. 2019;26:27–34. doi:10.1016/j.chembiol.2018.10.003.
  • Jukes CA, Ijaz, U. Z., Buckley, A., Spencer, J., Irvine, J., Candlish, D. & Douce, G. Bile salt metabolism is not the only factor contributing to Clostridioides (Clostridium) difficile disease severity in the murine model of disease. Gut Microbes. 2020;11(481–496). doi:10.1080/19490976.2019.1678996
  • Seekatz AM, Theriot, C. M., Molloy, C. T., Wozniak, K. L., Bergin, I. L., & Young, V. B. Fecal microbiota transplantation eliminates clostridium difficile in a murine model of relapsing disease. Infect Immun. 2015;83(3838–3846). doi:10.1128/IAI.00459-15
  • Mullish BH, McDonald, J. A., Pechlivanis, A., Allegretti, J. R., Kao, D., Barker, G. F. & Marchesi, J. R. Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection. Gut. 2019;68(1791–1800). doi:10.1136/gutjnl-2018-317842
  • Li X, Kang, Y., Huang, Y., Xiao, Y., Song, L., Lu, S., & Ren, Z. A strain of Bacteroides thetaiotaomicron attenuates colonization of Clostridioides difficile and affects intestinal microbiota and bile acids profile in a mouse model. Biomed Pharmacother. 2021;137(111290). doi:10.1016/j.biopha.2021.111290
  • Hryckowian AJ, Van Treuren, W., Smits, S. A., Davis, N. M., Gardner, J. O., Bouley, D. M., & Sonnenburg, J. L. Microbiota-accessible carbohydrates suppress Clostridium difficile infection in a murine model. Nat Microbiol. 2018;3(662–669). doi:10.1038/s41564-018-0150-6
  • Zhang W, Zou, G., Li, B., Du, X., Sun, Z., Sun, Y., & Jiang, X. Fecal microbiota transplantation (FMT) alleviates experimental colitis in mice by gut microbiota regulation. J Microbiol Biotechnol. 2020;30(1132–1141). doi:10.4014/jmb.2002.02044
  • Varga A, Kocsis, B., Sipos, D., Kása, P., Vigvári, S., Pál, S. & Péterfi, Z. How to apply FMT more effectively, conveniently and flexible - a comparison of FMT methods. Front Cell Infect Microbiol. 2021;11(657320). doi:10.3389/fcimb.2021.657320
  • (USA), F. a. D. A. REBYOTA, https://www.fda.gov/vaccines-blood-biologics/vaccines/rebyota (2022).
  • Khoruts A, Staley C, Sadowsky MJ. Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology. Nat Rev Gastroenterol Hepatol. 2021;18(67–80). doi:10.1038/s41575-020-0350-4.
  • Nooij S, Ducarmon, Q. R., Laros, J. F., Zwittink, R. D., Norman, J. M., Smits, W. K. & Kuijper, E. J. Fecal microbiota transplantation influences procarcinogenic Escherichia coli in Recipient recurrent clostridioides difficile patients. Gastroenterology. 2021;161:1218–1228. doi:10.1053/j.gastro.2021.06.009.
  • Brandt LJ, Aroniadis, O. C., Mellow, M., Kanatzar, A., Kelly, C., Park, T. & Surawicz, C. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(1079–1087). doi:10.1038/ajg.2012.60
  • van Beurden YH, de Groot, P. F., van Nood, E., Nieuwdorp, M., Keller, J. J., & Goorhuis, A. Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection. United European Gastroenterol J. 2017;5(868–879). doi:10.1177/2050640616678099
  • Jalanka J, Hillamaa, R. Satokari, E. Mattila, V‐J. Anttila, and P. Arkkila. The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2018;47(371–379). doi:10.1111/apt.14443
  • Petrof EO, Gloor, G. B., Vanner, S. J., Weese, S. J., Carter, D., Daigneault, M. C. & Allen-Vercoe, E. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome. 2013;1(3). doi:10.1186/2049-2618-1-3
  • Lawley TD, Clare, S., Walker, A. W., Stares, M. D., Connor, T. R., Raisen, C. & Dougan, G. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog. 2012;8(e1002995). doi:10.1371/journal.ppat.1002995
  • Pereira FC, Wasmund, K., Cobankovic, I., Jehmlich, N., Herbold, C. W., Lee, K. S. & Berry, D. Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization. Nat Commun. 2020;11(5104). doi:10.1038/s41467-020-18928-1
  • Nightingale KK, Schukken, Y. H., Nightingale, C. R., Fortes, E. D., Ho, A. J., Her, Z. & Wiedmann, M. Ecology and transmission of Listeria monocytogenes infecting ruminants and in the farm environment. Appl Environ Microbiol. 2004;70(4458–4467). doi:10.1128/AEM.70.8.4458-4467.2004
  • Bucur FI, Grigore-Gurgu L, Crauwels P, Riedel CU, Nicolau AI. Resistance of Listeria monocytogenes to stress conditions encountered in food and food processing environments. Front Microbiol. 2018;9(2700). doi:10.3389/fmicb.2018.02700.
  • Silk BJ, Date, K. A., Jackson, K. A., Pouillot, R., Holt, K. G., Graves, L. M. & Mahon, B. E. Invasive listeriosis in the foodborne diseases active surveillance network (FoodNet), 2004-2009: further targeted prevention needed for higher-risk groups. Clin Infect Dis. 2012;54(Suppl 5):S396–404. doi:10.1093/cid/cis268.
  • Churchill KJ, Sargeant JM, Farber JM, O’Connor AM. Prevalence of listeria monocytogenes in select ready-to-eat foods-deli meat, soft cheese, and packaged salad: a systematic review and meta-analysis. J Food Prot. 2019;82(344–357). doi:10.4315/0362-028X.JFP-18-158.
  • Swaminathan B, Gerner-Smidt P. The epidemiology of human listeriosis. Microbes Infect. 2007;9(1236–1243). doi:10.1016/j.micinf.2007.05.011.
  • Maury MM, Tsai, Y. H., Charlier, C., Touchon, M., Chenal-Francisque, V., Leclercq, A. & Lecuit, M. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. Nat Genet. 2016;48(308–313). doi:10.1038/ng.3501
  • Radoshevich L, Cossart P. Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis. Nat Rev Microbiol. 2018;16(32–46). doi:10.1038/nrmicro.2017.126.
  • Nikitas G, Deschamps, C., Disson, O., Niault, T., Cossart, P., & Lecuit, M. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin. J Exp Med. 2011;208(2263–2277). doi:10.1084/jem.20110560
  • Sheehan B, Klarsfeld A, Msadek T, Cossart P. Differential activation of virulence gene expression by PrfA, the Listeria monocytogenes virulence regulator. J Bacteriol. 1995;177(6469–6476). doi:10.1128/jb.177.22.6469-6476.1995.
  • Ollinger J, Bowen B, Wiedmann M, Boor KJ, Bergholz TM. Listeria monocytogenes sigmaB modulates PrfA-mediated virulence factor expression. Infect Immun. 2009;77(2113–2124). doi:10.1128/IAI.01205-08.
  • Gahan CG, Hill C. Listeria monocytogenes: survival and adaptation in the gastrointestinal tract. Front Cell Infect Microbiol. 2014;4(9). doi:10.3389/fcimb.2014.00009.
  • Sauer JD, Herskovits AA, O’Riordan MXD. Metabolism of the gram-positive bacterial pathogen listeria monocytogenes. Microbiol Spectr. 2019:7. doi:10.1128/microbiolspec.GPP3-0066-2019.
  • Joseph B, Mertins, S., Stoll, R., Schar, J., Umesha, K. R., Luo, Q. & Goebel, W. Glycerol metabolism and PrfA activity in Listeria monocytogenes. J Bacteriol. 2008;190(5412–5430). doi:10.1128/JB.00259-08
  • Tiensuu T, Guerreiro DN, Oliveira AH, O’Byrne C, Johansson J. Flick of a switch: regulatory mechanisms allowing Listeria monocytogenes to transition from a saprophyte to a killer. Microbiology (Reading). 2019;165(819–833). doi:10.1099/mic.0.000808.
  • Czuprynski CJ, Balish E. Pathogenesis of Listeria monocytogenes for gnotobiotic rats. Infect Immun. 1981;32(323–331). doi:10.1128/iai.32.1.323-331.1981.
  • Bambirra FH, Lima, K. G. C., Franco, B. D. G. D. M., Cara, D. C., Nardi, R. M. D., Barbosa, F. H. F., & Nicoli, J. R. Protective effect of Lactobacillus sakei 2a against experimental challenge with Listeria monocytogenes in gnotobiotic mice. Lett Appl Microbiol. 2007;45(663–667). doi:10.1111/j.1472-765X.2007.02250.x
  • Archambaud C, Nahori, M. A., Soubigou, G., Bécavin, C., Laval, L., Lechat, P., & Cossart, P. Impact of lactobacilli on orally acquired listeriosis. Proc Natl Acad Sci U S A. 2012;109:16684–16689. doi:10.1073/pnas.1212809109.
  • Corr SC, Hill C, Gahan CG. Understanding the mechanisms by which probiotics inhibit gastrointestinal pathogens. Adv Food Nutr Res. 2009;56(1–15). doi:10.1016/S1043-4526(08)00601-3.
  • Brandl K, Plitas G, Schnabl B, DeMatteo RP, Pamer EG. MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med. 2007;204(1891–1900). doi:10.1084/jem.20070563.
  • Las Heras V, Clooney, A. G., Ryan, F. J., Cabrera-Rubio, R., Casey, P. G., Hueston, C. M. & Gahan, C. G. Short-term consumption of a high-fat diet increases host susceptibility to Listeria monocytogenes infection. Microbiome. 2019;7(7). doi:10.1186/s40168-019-0621-x
  • van Ampting MT, Loonen, L. M., Schonewille, A. J., Konings, I., Vink, C., Iovanna, J. & Bovee-Oudenhoven, I. M. Intestinally secreted C-type lectin Reg3b attenuates salmonellosis but not listeriosis in mice. Infect Immun. 2012;80(1115–1120). doi:10.1128/IAI.06165-11
  • Rolhion N, Chassaing, B., Nahori, M. A., De Bodt, J., Moura, A., Lecuit, M. & Cossart, P. A listeria monocytogenes bacteriocin can target the commensal prevotella copri and modulate intestinal infection. Cell Host Microbe. 2019;26:691–701. doi:10.1016/j.chom.2019.10.016.
  • Cotter PD, Draper, L. A., Lawton, E. M., Daly, K. M., Groeger, D. S., Casey, P. G. & Hill, C. Listeriolysin S, a novel peptide haemolysin associated with a subset of lineage I Listeria monocytogenes. PLoS Pathog. 2008;4(e1000144). doi:10.1371/journal.ppat.1000144
  • Quereda JJ, Meza-Torres J, Cossart P, Listeriolysin P-CJ. S: a bacteriocin from epidemic Listeria monocytogenes strains that targets the gut microbiota. Gut Microbes. 2017;8(384–391). doi:10.1080/19490976.2017.1290759.
  • Quereda JJ, Dussurget, O., Nahori, M. A., Ghozlane, A., Volant, S., Dillies, M. A. & Pizarro-Cerda, J. Bacteriocin from epidemic Listeria strains alters the host intestinal microbiota to favor infection. Proc Natl Acad Sci U S A. 2016;113(5706–5711). doi:10.1073/pnas.1523899113
  • Becattini S, Littmann, E. R., Carter, R. A., Kim, S. G., Morjaria, S. M., Ling, L. & Pamer, E. G. Commensal microbes provide first line defense against Listeria monocytogenes infection. J Exp Med. 2017;214(1973–1989). doi:10.1084/jem.20170495
  • Corr SC, Gahan CG, Hill C. Impact of selected Lactobacillus and Bifidobacterium species on Listeria monocytogenes infection and the mucosal immune response. FEMS Immunol Med Microbiol. 2007;50(380–388). doi:10.1111/j.1574-695X.2007.00264.x.
  • Mathipa MG, Bhunia AK, Thantsha MS. Internalin AB-expressing recombinant Lactobacillus casei protects Caco-2 cells from Listeria monocytogenes-induced damages under simulated intestinal conditions. PLoS One. 2019;14(e0220321). doi:10.1371/journal.pone.0220321.
  • Drolia R, Amalaradjou, M. A. R., Ryan, V., Tenguria, S., Liu, D., Bai, X. & Bhunia, A. K. Receptor-targeted engineered probiotics mitigate lethal Listeria infection. Nat Commun. 2020;11(6344). doi:10.1038/s41467-020-20200-5
  • Bou Ghanem EN, Jones, G. S., Myers-Morales, T., Patil, P. D., Hidayatullah, A. N., & D'Orazio, S. E. InlA promotes dissemination of Listeria monocytogenes to the mesenteric lymph nodes during food borne infection of mice. PLoS Pathog. 2012;8(e1003015). doi:10.1371/journal.ppat.1003015
  • Hoelzer K, Pouillot R, Dennis S. Animal models of listeriosis: a comparative review of the current state of the art and lessons learned. Vet Res. 2012;43(18). doi:10.1186/1297-9716-43-18.
  • Lecuit M, Vandormael-Pournin, S., Lefort, J., Huerre, M., Gounon, P., Dupuy, C. & Cossart, P. A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier. Science. 2001;292(1722–1725). doi:10.1126/science.1059852
  • Disson O, Grayo, S., Huillet, E., Nikitas, G., Langa-Vives, F., Dussurget, O. & Lecuit, M. Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature. 2008;455(1114–1118). doi:10.1038/nature07303
  • Schubert WD, Urbanke, C., Ziehm, T., Beier, V., Machner, M. P., Domann, E. & Heinz, D. W. Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin. Cell. 2002;111(825–836). doi:10.1016/s0092-8674(02)01136-4
  • Monk IR, Casey PG, Hill C, Gahan CG. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model. BMC Microbiol. 2010;10(318). doi:10.1186/1471-2180-10-318.
  • Tsai YH, Disson O, Bierne H, Lecuit M. Murinization of internalin extends its receptor repertoire, altering Listeria monocytogenes cell tropism and host responses. PLoS Pathog. 2013;9(e1003381). doi:10.1371/journal.ppat.1003381.
  • Cossart P. Molecular and cellular basis of the infection by Listeria monocytogenes: an overview. International Journal of Medical Microbiology. 2001;291(401–409). doi:10.1078/1438-4221-00146.
  • Roldgaard BB, Andersen JB, Hansen TB, Christensen BB, Licht TR. Comparison of three Listeria monocytogenes strains in a Guinea-pig model simulating food-borne exposure. FEMS Microbiol Lett. 2009;291(88–94). doi:10.1111/j.1574-6968.2008.01439.x.
  • Pitts MG, D’Orazio SEF. A comparison of oral and intravenous mouse models of listeriosis. Pathogens. 2018:7. doi:10.3390/pathogens7010013.
  • Holch A, Ingmer H, Licht TR, Gram L. Listeria monocytogenes strains encoding premature stop codons in inlA invade mice and Guinea pig fetuses in orally dosed dams. J Med Microbiol. 2013;62(1799–1806). doi:10.1099/jmm.0.057505-0.
  • Alam MS, Costales, M., Cavanaugh, C., Pereira, M., Gaines, D., & Williams, K. Oral exposure to Listeria monocytogenes in aged IL-17RKO mice: a possible murine model to study listeriosis in susceptible populations. Microb Pathog. 2016;99(236–246). doi:10.1016/j.micpath.2016.08.035
  • Mitchell PS, Roncaioli, J. L., Turcotte, E. A., Goers, L., Chavez, R. A., Lee, A. Y. & Vance, R. E. NAIP–NLRC4-deficient mice are susceptible to shigellosis. eLife. 2020;9(e59022). doi:10.7554/eLife.59022
  • Martz SL, McDonald, J. A., Sun, J., Zhang, Y. G., Gloor, G. B., Noordhof, C. & Petrof, E. O. Administration of defined microbiota is protective in a murine Salmonella infection model. Sci Rep. 2015;5(16094). doi:10.1038/srep16094