Colonization of commensal and pathogenic bacteria begins with the adherence on several biological components, such as mucus, epithelial cells, and lamina propria of the gastrointestinal tract (GIT) in human and animal hosts.Citation1,2 Major driving forces behind to strengthen the binding at the interface of bacteria and hosts are protein-protein and protein-carbohydrate interactions, due mainly to distribution patterns of glycolipids, sugar chains, and proteins on the surface layers of the bacteria and the hosts.Citation3,4 In terms of proteins involved with the host-bacterial interaction, commensal and pathogenic bacteria largely share molecular mechanisms of the initial steps of adherence to the hosts, indicating the presence of common adhesion proteins on their surfaces, which can interact with specific receptors or soluble macromolecules in the hosts.Citation2 For example, both commensal and pathogenic bacteria have similar proteinaceous structures, called pili, fimbriae, and flagella, which are filamentous architectures composed by assembling of one or more subunit proteins that protrude on the bacterial cell surface.Citation5,6,7
Historically, such bacterial filaments have been well studied on pathogens who use different types of pilus, such as chaperone-usher pili,Citation8 curli pili,Citation9 and type IV piliCitation10 to attach onto the hosts from the “safe” distance circumventing their defense system. In fact, the binding of pilus proteins to the host cell receptors elicits different responses, leading to cytoprotection and remodeling of the host cells,Citation11,12 inflammation,Citation13 and internalization of the bacteria.Citation14 The sortase-dependent pili, which had been previously dedicated to pathogenic Gram-positive bacteria, e.g., Actinomyces,Citation15 Corynebacterium,Citation16,17 Clostridia,Citation16,17 Enterococci,Citation18 and Streptococcus,Citation19 have been recently found also in probiotic Lactobacillus rhamnosus GG and Bifidobacterium bifidum PRL2010, demonstrating that they were involved not only with adherence but also with favorable immune response of the host.Citation20,21
Nonpilus adhesins of several bacteria also play pivotal roles in adherence to the host and its immune response. In pathogenic bacteria, trimeric autotransporter adhesinsCitation22 and adhesins belonging to a protein family termed microbial surface components recognizing adhesive matrix molecules (MSCRAMMs)Citation23 were found as virulence factors in Gram-negative and -positive bacteria, respectively. MSCRAMMs specifically recognize extracellular matrix (ECM) glycoproteins and they possess conserved LPXTG or related motifs responsible for anchoring the cell wall by the action of sortase.Citation24 A unique structure of MSCRAMMs, which consists of two separate domains and a highly flexible linker, enables them to take open and closed apo forms and to capture the ligand molecule at the interspace of the two domains.Citation25,26 Irrespective of Gram-stainability and pathogenicity, several moonlighting proteins, which show multiple functions in different cellular localization,Citation27 have been characterized as universal nonpilus adhesins. In contrast to MSCRAMMs, moonlighting proteins are supposed to be anchorless surface proteins. The canonical functions of moonlighting proteins attribute to the essential cellular metabolic processes, such as glycolysis,Citation28 protein synthesis and quality control,Citation29 and redox homeostasis;Citation30 however, some of them act as adhesins with a wide variety of affinities for mucin, host cells, carbohydrates, ECM glycoproteins, and plasminogen/plasmin when they emerged on the bacterial cell surface, although the exhibition mechanism remains controversial.Citation31
ECM in the lamina propria of the GIT is a complex of glycosaminoglycans and ECM glycoproteins, including collagen, fibronectin, laminin, elastin, thrombospondin, tenascin, and nidogen, secreted by epithelial and mesenchymal cells.Citation32,33 Cells are surrounded by ECM and hence embedded in the tissue, giving physical strength and flexibility, and furthermore, ECM modulates differentiation, migration, polarity, proliferation, and vitality of the cells, by stimulating cell signaling pathways via proteoglycan-cytoskeletal integrin-growth factor receptor axis.Citation34 Under physiologically normal conditions, the major part of ECM underlie the epithelial cells in the GIT, but the localized exposure of ECM to the intestinal lumen occurs transiently by cell shedding during the turnover.Citation35 Moreover, ECM seems to be extensively exposed by trauma and bacterial/viral infections,Citation36 providing a favorable target for pathogenic bacteria to adhere. In this context, commensal or probiotic bacteria capable of adhering ECM may compete with pathogens to colonize on the host surface, and hence prevent their invasion further deep into the tissue.Citation37 Indeed, commensal and pathogenic bacteria express several cell surface moonlighting proteins in common that bind to the ECM glycoproteins, e.g., enolase,Citation38,39 glyceraldehyde-3-phosphate dehydrogenase,Citation39,40 and pyruvate dehydrogenase,Citation41,42 supporting possibly the feasibility of so-called “competitive exclusion”.
In this issue of Virulence, Lehri et al.Citation43 demonstrated Lactobacillus fermentum 3872 competed against Campylobacter jejuni for binding type I collagen. They showed that cell numbers of Campylobacter strains which adhered to collagen I immobilized on ELISA plates were significantly decreased when L. fermentum 3872 was co-cultured in 5- to 10-times higher population over C. jejuni. Furthermore, by co-immunoprecipitation, mass spectrometry, and ELISA techniques, they revealed a unique collagen binding protein anchoring on the bacterial cell surface of L. fermentum 3872 was a major player for the competitive action, whereas flagellin was found for binding collagen I in C. jejuni. Collagen I is well known as a component of ECM of the lamina propria, but it is also likely to present in submucosa, which is a layer of tissue that connects mucosa and muscularis in the GIT of primates.Citation44 Calabi et al.Citation45 reported Clostridium diffcile adhered to collagen I via its surface layer proteins, and hence collagen I is potential to be a good target for competitive exclusion of pathogens that adhere to ECM and/or submucosa in the GIT. To ensure the results shown by Lehri et al.,Citation43 in vivo experiments should be performed in the future as was reported by Nishiyama et al.,Citation46 in which Lactobacillus gasseri SBT2055 reduced C. jejuni infection in chicken by competitive binding to the host cells and/or co-aggregation with the pathogen in mediation of cell-surface aggregation-promoting factors.
One of what makes it difficult to illustrate entire mechanism of host-bacterial interaction is a complexity of adhesins present on the bacterial cell surface in strain- and environment-dependent manners. Therefore, selection of suitable probiotics or the rational design of optimum conditions to achieve the ideal competitive exclusion seems too ambitious, to date. After all, such a step-by-step approach that accumulates individual data towards adhesins and natural antibacterial substances in probiotics as reported by Lehri et al.Citation43 should be a sound method to pursue suitable anti-pathogenic probiotics, leading to the reduction of antibiotics usage in combat with pathogens.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
References
- Pizarro-Cerdá J, Cossart P. Bacterial adhesion and entry into host cells. Cell. 2006;124:715–27
- Kline KA, Fälker S, Dahlberg S, Normark S, Henriques-Normark B. Bacterial adhesins in host-microbe interactions. Cell Host Microbe. 2009;5:580–92
- Westerlund B, Korhonen TK. Bacterial proteins binding to the mammalian extracellular matrix. Mol Microbiol. 1993;9:687–94. PMID:7901732
- Iñiguez-Palomares C, Jiménez-Flores R, Vázquez-Moreno L, Ramos-Clamont-Montfort G, Acedo-Félix E. Protein-carbohydrate interactions between Lactobacillus salivarius and pig mucins. J Anim Sci. 2011;89:3125–31. PMID:21622872
- Li T, Khah MK, Slavnic S, Johansson I, Strömberg N. Different type 1 fimbrial genes and tropisms of commensal and potentially pathogenic Actinomyces spp. with different salivary acidic proline-rich protein and statherin ligand specificities. Infect Immun. 2001;69:7224–33. PMID:11705891
- Andersen-Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A. Evasion of Toll-like receptor 5 by flagellated bacteria. Proc Natl Acad Sci U S A. 2005;102:9247–52. PMID:15956202
- Rendón MA, Saldaña Z, Erdem AL, Monteiro-Neto V, Vázquez A, Kaper JB, Puente JL, Girón JA. Commensal and pathogenic Escherichia coli use a common pilus adherence factor for epithelial cell colonization. Proc Natl Acad Sci U S A. 2007;104:10637–42. PMID:17563352
- Remaut H, Tang C, Henderson NS, Pinkner JS, Wang T, Hultgren SJ, Thanassi DG, Waksman G, Li H. Fiber formation across the bacterial outer membrane by the chaperone/usher pathway. Cell. 2008;133:640–52. PMID:18485872
- Olsén A, Jonsson A, Normark S. Fibronectin binding mediated by a novel class of surface organelles on Escherichia coli. Nature. 1989;338:652–5. PMID:2649795
- Bieber D, Ramer SW, Wu CY, Murray WJ, Tobe T, Fernandez R, Schoolnik GK. Type IV pili, transient bacterial aggregates, and virulence of enteropathogenic Escherichia coli. Science. 1998;280:2114–8. doi:https://doi.org/10.1126/science.280.5372.2114. PMID:9641917
- Howie HL, Glogauer M, So M. The N. gonorrhoeae type IV pilus stimulates mechanosensitive pathways and cytoprotection through a pilT-dependent mechanism. PLoS Biol. 2005;3:e100. doi:https://doi.org/10.1371/journal.pbio.0030100. PMID:15769184
- Shifrin DA, Jr, Crawley SW, Grega-Larson NE, Tyska MJ. Dynamics of brush border remodeling induced by enteropathogenic E. coli. Gut Microbes. 2014;5:504–16. doi:https://doi.org/10.4161/gmic.32084. PMID:25076126
- Barocchi MA, Ries J, Zogaj X, Hemsley C, Albiger B, Kanth A, Dahlberg S, Fernebro J, Moschioni M, Masignani V, et al. A pneumococcal pilus influences virulence and host inflammatory responses. Proc Natl Acad Sci U S A. 2006;103:2857–62. doi:https://doi.org/10.1073/pnas.0511017103. PMID:16481624
- Eugène E, Hoffmann I, Pujol C, Couraud PO, Bourdoulous S, Nassif X. Microvilli-like structures are associated with the internalization of virulent capsulated Neisseria meningitidis into vascular endothelial cells. J Cell Sci. 2002;115:1231–41. PMID:11884522
- Mishra A, Das A, Cisar JO, Ton-That H. Sortase-catalyzed assembly of distinct heteromeric fimbriae in Actinomyces naeslundii. J Bacteriol. 2007;189:3156–65. doi:https://doi.org/10.1128/JB.01952-06. PMID:17277070
- Ton-That H, Schneewind O. Assembly of pili on the surface of Corynebacterium diphtheriae. Mol Microbiol. 2003;50:1429–38. doi:https://doi.org/10.1046/j.1365-2958.2003.03782.x. PMID:14622427
- Gaspar AH, Ton-That H. Assembly of distinct pilus structures on the surface of Corynebacterium diphtheriae. J Bacteriol. 2006;188:1526–33. doi:https://doi.org/10.1128/JB.188.4.1526-1533.2006. PMID:16452436
- Sillanpää J, Nallapareddy SR, Singh KV, Prakash VP, Fothergill T, Ton-That H, Murray BE. Characterization of the ebp(fm) pilus-encoding operon of Enterococcus faecium and its role in biofilm formation and virulence in a murine model of urinary tract infection. Virulence. 2010;1:236–46. doi:https://doi.org/10.4161/viru.1.4.11966. PMID:20676385
- Rosini R, Rinaudo CD, Soriani M, Lauer P, Mora M, Maione D, Taddei A, Santi I, Ghezzo C, Brettoni C, et al. Identification of novel genomic islands coding for antigenic pilus-like structures in Streptococcus agalactiae. Mol Microbiol. 2006;61:126–41. doi:https://doi.org/10.1111/j.1365-2958.2006.05225.x. PMID:16824100
- Lebeer S, Claes I, Tytgat HL, Verhoeven TL, Marien E, von Ossowski I, Reunanen J, Palva A, Vos WM, Keersmaecker SC, Vanderleyden J. Functional analysis of Lactobacillus rhamnosus GG pili in relation to adhesion and immunomodulatory interactions with intestinal epithelial cells. Appl Environ Microbiol. 2012;78:185–93. doi:https://doi.org/10.1128/AEM.06192-11. PMID:22020518
- Turroni F, Serafini F, Foroni E, Duranti S, O'Connell Motherway M, Taverniti V, Mangifesta M, Milani C, Viappiani A, et al. Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions. Proc Natl Acad Sci U S A. 2013;110:11151–6. doi:https://doi.org/10.1073/pnas.1303897110. PMID:23776216
- Scarselli M, Serruto D, Montanari P, Capecchi B, Adu-Bobie J, Veggi D, Rappuoli R, Pizza M, Aricò B. Neisseria meningitidis NhhA is a multifunctional trimeric autotransporter adhesin. Mol Microbiol. 2006;61:631–44. doi:https://doi.org/10.1111/j.1365-2958.2006.05261.x. PMID:16803596
- Patti JM, Allen BL, McGavin MJ, Höök M. MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol. 1994;48:585–617. doi:https://doi.org/10.1146/annurev.mi.48.100194.003101. PMID:7826020
- Ton-That H, Mazmanian SK, Faull KF, Schneewind O. Anchoring of surface proteins to the cell wall of Staphylococcus aureus. Sortase catalyzed in vitro transpeptidation reaction using LPXTG peptide and NH(2)-Gly(3) substrates. J Biol Chem. 2000;275:9876–81. doi:https://doi.org/10.1074/jbc.275.13.9876. PMID:10734144
- Zong Y, Xu Y, Liang X, Keene DR, Höök A, Gurusiddappa S, Höök M, Narayana SV. A ‘Collagen Hug’ model for Staphylococcus aureus CNA binding to collagen. EMBO J. 2005;24:4224–36. doi:https://doi.org/10.1038/sj.emboj.7600888. PMID:16362049
- Bowden MG, Heuck AP, Ponnuraj K, Kolosova E, Choe D, Gurusiddappa S, Narayana SV, Johnson AE, Höök M. Evidence for the “dock, lock, and latch” ligand binding mechanism of the staphylococcal microbial surface component recognizing adhesive matrix molecules (MSCRAMM) SdrG. J Biol Chem. 2008;283:638–47. doi:https://doi.org/10.1074/jbc.M706252200. PMID:17991749
- Jeffery CJ. Moonlighting proteins. Trends Biochem Sci. 1999;24:8–11. doi:https://doi.org/10.1016/S0968-0004(98)01335-8. PMID:10087914
- Pitarch A, Sánchez M, Nombela C, Gil C. Sequential fractionation and two-dimensional gel analysis unravels the complexity of the dimorphic fungus Candida albicans cell wall proteome. Mol Cell Proteomics. 2002;1:967–82. doi:https://doi.org/10.1074/mcp.M200062-MCP200. PMID:12543933
- Schaumburg J, Diekmann O, Hagendorff P, Bergmann S, Rohde M, Hammerschmidt S, Jänsch L, Wehland J, Kärst U. The cell wall subproteome of Listeria monocytogenes. Proteomics. 2004;4:2991–3006. doi:https://doi.org/10.1002/pmic.200400928. PMID:15378750
- Reddy VM, Suleman FG. Mycobacterium avium-superoxide dismutase binds to epithelial cell aldolase, glyceraldehyde-3-phosphate dehydrogenase and cyclophilin A. Microb Pathog. 2004;36:67–74. doi:https://doi.org/10.1016/j.micpath.2003.09.005. PMID:14687559
- Kainulainen V, Korhonen TK. Dancing to another tune-adhesive moonlighting proteins in bacteria. Biology (Basel). 2014;3:178–204. PMID:24833341
- Beaulieu JF, Vachon PH, Chartrand S. Immunolocalization of extracellular matrix components during organogenesis in the human small intestine. Anat Embryol (Berl). 1991;183:363–9. doi:https://doi.org/10.1007/BF00196837. PMID:1714254
- Gillessen A, Voss B, Rauterberg J, Domschke W. Distribution of collagen types I, III, and IV in peptic ulcer and normal gastric mucosa in man. Scand J Gastroenterol. 1993;28:688–9. doi:https://doi.org/10.3109/00365529309098273. PMID:8210983
- Kim SH, Turnbull J, Guimond S. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol. 2011;209:139–51. doi:https://doi.org/10.1530/JOE-10-0377. PMID:21307119
- Watson AJ, Duckworth CA, Guan Y, Montrose MH. Mechanisms of epithelial cell shedding in the Mammalian intestine and maintenance of barrier function. Ann N Y Acad Sci. 2009;1165:135–42. doi:https://doi.org/10.1111/j.1749-6632.2009.04027.x. PMID:19538298
- Ljungh A, Moran AP, Wadström T. Interactions of bacterial adhesins with extracellular matrix and plasma proteins: pathogenic implications and therapeutic possibilities. FEMS Immunol Med Microbiol. 1996;16:117–26. doi:https://doi.org/10.1111/j.1574-695X.1996.tb00128.x. PMID:8988392
- Servin AL. Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiol Rev. 2004;28:405–40. doi:https://doi.org/10.1016/j.femsre.2004.01.003. PMID:15374659
- Antikainen J, Kuparinen V, Lähteenmäki K, Korhonen TK. Enolases from Gram-positive bacterial pathogens and commensal lactobacilli share functional similarity in virulence-associated traits. FEMS Immunol Med Microbiol. 2007;51:526–34. doi:https://doi.org/10.1111/j.1574-695X.2007.00330.x. PMID:17892475
- Glenting J, Beck HC, Vrang A, Riemann H, Ravn P, Hansen AM, Antonsson M, Ahrné S, Israelsen H, Madsen S. Anchorless surface associated glycolytic enzymes from Lactobacillus plantarum 299v bind to epithelial cells and extracellular matrix proteins. Microbiol Res. 2013;168:245–53. doi:https://doi.org/10.1016/j.micres.2013.01.003. PMID:23395591
- Pancholi V, Fischetti VA. A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity. J Exp Med. 1992;176:415–26. doi:https://doi.org/10.1084/jem.176.2.415. PMID:1500854
- Dallo SF, Kannan TR, Blaylock MW, Baseman JB. Elongation factor Tu and E1 beta subunit of pyruvate dehydrogenase complex act as fibronectin binding proteins in Mycoplasma pneumoniae. Mol Microbiol. 2002;46:1041–51. doi:https://doi.org/10.1046/j.1365-2958.2002.03207.x. PMID:12421310
- Vastano V, Salzillo M, Siciliano RA, Muscariello L, Sacco M, Marasco R. The E1 beta-subunit of pyruvate dehydrogenase is surface-expressed in Lactobacillus plantarum and binds fibronectin. Microbiol Res. 2014;169:121–7. doi:https://doi.org/10.1016/j.micres.2013.07.013. PMID:24054819
- Lehri B, Seddon AM, Karlyshev AV. Lactobacillus fermentum 3872 as a potential tool for combatting Campylobacter jejuni infections. Virulence. 2017:1–8. doi:https://doi.org/10.1080/21505594.2017.1362533. PMID:28766992
- Mello MFVd, Pissinatti A, Ferreira AMR. Distribution of collagen types I, III, and IV in gastric tissue of marmosets (Callithrix spp., Callitrichidae: Primates). Pesquisa Veterinária Brasileira. 2010;30:317–20. doi:https://doi.org/10.1590/S0100-736X2010000400006.
- Calabi E, Calabi F, Phillips AD, Fairweather NF. Binding of Clostridium difficile surface layer proteins to gastrointestinal tissues. Infect Immun. 2002;70:5770–8. doi:https://doi.org/10.1128/IAI.70.10.5770-5778.2002. PMID:12228307
- Nishiyama K, Nakazato A, Ueno S, Seto Y, Kakuda T, Takai S, Yamamoto Y, Mukai T. Cell surface-associated aggregation-promoting factor from Lactobacillus gasseri SBT2055 facilitates host colonization and competitive exclusion of Campylobacter jejuni. Mol Microbiol. 2015;98:712–26. doi:https://doi.org/10.1111/mmi.13153.