Tobacco Hornworm (Manduca sexta) caterpillars as a novel host model for the study of fungal virulence and drug efficacy

References

• Brown GD, Denning DW, Gow NAR, et al. Hidden killers: human fungal infections. Sci Transl Med. 2012;4:165rv13.
   PubMed Web of Science ®Google Scholar
• Harsha MV, International SV. Emerging fungal pathogens-a major threat to human life. IJPSR. 2017;8:1923–1934.
   Google Scholar
• Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit Rev Microbiol. 2010;36:1–53.
   PubMed Web of Science ®Google Scholar
• Nyazika TK, Tatuene JK, Kenfak-Foguena A, et al. Epidemiology and aetiologies of cryptococcal meningitis in Africa, 1950–2017: protocol for a systematic review. BMJ Open. 2018;8:e020654.
   PubMed Web of Science ®Google Scholar
• Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Inf Dis. 2009;48:503–535.
   PubMed Web of Science ®Google Scholar
• Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20:133–163.
   PubMed Web of Science ®Google Scholar
• Jensen RH, Johansen HK, Søes LM, et al. Posttreatment antifungal resistance among colonizing Candida isolates in candidemia patients: results from a systematic multicenter study. Antimicrob Agents Chemother. 2016;60:1500–1508.
   Web of Science ®Google Scholar
• Satoh K, Makimura K, Hasumi Y, et al. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009;53:41–44.
   PubMed Web of Science ®Google Scholar
• Schelenz S, Hagen F, Rhodes JL, et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control. 2016;5:1–7.
   PubMed Web of Science ®Google Scholar
• Bidaud AL, Chowdhary A, Dannaoui E. Candida auris: an emerging drug resistant yeast – A mini-review. J Mycol Med. 2018;28:568–573.
   PubMed Web of Science ®Google Scholar
• Zaoutis TE, Argon J, Chu J, et al. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis. 2005;41:1232–1239.
   PubMed Web of Science ®Google Scholar
• Segal E, Frenkel M. Experimental in vivo models of candidiasis. JoF. 2018;4:21.
   Web of Science ®Google Scholar
• Zaragoza O, Alvarez M, Telzak A, et al. The relative susceptibility of mouse strains to pulmonary Cryptococcus neoformans infection is associated with pleiotropic differences in the immune response. Infect Immun. 2007;75:2729–2739.
   PubMed Web of Science ®Google Scholar
• Perfect JR, Lang SD, Durack DT. Chronic cryptococcal meningitis: A new experimental model in rabbits. Am J Pathol. 1980;101:177–194.
   PubMed Web of Science ®Google Scholar
• Ray WA, O’Day DM, Head WS, et al. Variability in isolate recovery rates from multiple and single breeds of outbred pigmented rabbits in an experimental model of Candida keratitis. Curr Eye Res. 2009;3:949–953.
   Google Scholar
• Mylonakis E, Ausubel FM, Perfect JR, et al. Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis. PNAS. 2002;99:15675–15680.
   PubMed Web of Science ®Google Scholar
• Fuchs BB, O’Brien E, Khoury EJB, et al. Methods for using Galleria mellonella as a model host to study fungal pathogenesis. Virulence. 2014;1:475–482.
   Google Scholar
• Pukkila-Worley R, Ausubel FM, Mylonakis E. Candida albicans infection of Caenorhabditis elegans induces antifungal immune defenses. PLoS Pathog. 2011;7:e1002074.
   PubMed Web of Science ®Google Scholar
• Chamilos G, Lionakis MS, Lewis RE, et al. Drosophila melanogaster as a facile model for large-scale studies of virulence mechanisms and antifungal drug efficacy in Candida species. J Infect Dis. 2006;193:1014–1022.
   PubMed Web of Science ®Google Scholar
• Ortega-Riveros M, De-la-Pinta I, Marcos-Arias C, et al. Usefulness of the non-conventional Caenorhabditis elegans model to assess Candida virulence. Mycopathologia. 2017;182:785–795.
   PubMed Web of Science ®Google Scholar
• Gago S, García-Rodas R, Cuesta I, et al. Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis virulence in the non-conventional host Galleria mellonella. Virulence. 2014;5:278–285.
   PubMed Web of Science ®Google Scholar
• Ames L, Duxbury S, Pawlowska B, et al. Galleria mellonella as a host model to study Candida glabrata virulence and antifungal efficacy. Virulence. 2017;8:1–9.
   PubMed Web of Science ®Google Scholar
• Desalermos A, Fuchs BB, Mylonakis E. Selecting an invertebrate model host for the study of fungal pathogenesis. PLoS Pathog. 2012;8:e1002451.
   PubMed Web of Science ®Google Scholar
• Mylonakis E, Aballay A. Worms and flies as genetically tractable animal models to study host-pathogen interactions. Infect Immun. 2005;73:3833–3841.
   PubMed Web of Science ®Google Scholar
• Vogel H, Altincicek B, Glöckner G, et al. A comprehensive transcriptome and immune- gene repertoire of the lepidopteran model host Galleria mellonella. BMC Genomics. 2011;12:308.
   PubMed Web of Science ®Google Scholar
• Lemaitre B, Nicolas E, Michaut L, et al. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86:973–983.
   PubMed Web of Science ®Google Scholar
• Kim DH, Feinbaum R, Alloing G, et al. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science. 2002;297:623–626.
   PubMed Web of Science ®Google Scholar
• Apidianakis Y, Rahme LG, Heitman J, et al. Challenge of Drosophila melanogaster with Cryptococcus neoformans and role of the innate immune response. Eukaryot Cell. 2004;3:413–419.
   PubMed Web of Science ®Google Scholar
• Alarco A-M, Marcil A, Chen J, et al. Immune-deficient Drosophila melanogaster: A model for the innate immune response to human fungal pathogens. J Immunol. 2004;172:5622–5628.
   PubMed Web of Science ®Google Scholar
• Quintin J, Asmar J, Matskevich AA, et al. The Drosophila Toll pathway controls but does not clear Candida glabrata infections. J Immunol. 2013;190:2818–2827.
   PubMed Web of Science ®Google Scholar
• Breger J, Fuchs BB, Aperis G, et al. Antifungal chemical compounds identified using a C. elegans pathogenicity assay. PLoS Pathog. 2007;3:e18.
   PubMed Web of Science ®Google Scholar
• Lange A, Beier S, Huson DH, et al. Genome sequence of Galleria mellonella (Greater Wax Moth). Genome Announc. 2018;6:61–62.
   Google Scholar
• Flowers RW, Entomologist RYF. Feeding on non-host plants by the Tobacco Hornworm (Manduca sexta (Lepidoptera: Sphingidae). JSTOR. 1982;65:523–530.
   Google Scholar
• Kanost MR, Arrese EL, Cao X, et al. Multifaceted biological insights from a draft genome sequence of the Tobacco Hornworm moth, Manduca sexta. Insect Biochem Mol Biol. 2016;76:118–147.
   PubMed Web of Science ®Google Scholar
• Flores-Escobar B, Rodríguez-Magadan H, Bravo A, et al. Differential role of Manduca sexta aminopeptidase-N and alkaline phosphatase in the mode of action of Cry1Aa, Cry1Ab, and Cry1Ac toxins from Bacillus thuringiensis. Appl Environ Microbiol. 2013;79:4543–4550.
   PubMed Web of Science ®Google Scholar
• Burke WG, Kaplanoglu E, Kolotilin I, et al. RNA interference in the Tobacco Hornworm, Manduca sexta, using plastid-encoded long double-stranded RNA. Front Plant Sci. 2019;10:313.
   PubMed Web of Science ®Google Scholar
• Eleftherianos I, Millichap PJ. ffrench-Constant RH, Reynolds SE. RNAi suppression of recognition protein mediated immune responses in the Tobacco Hornworm Manduca sexta causes increased susceptibility to the insect pathogen Photorhabdus. Dev Comp Immunol. 2006;30:1099–1107.
   PubMed Web of Science ®Google Scholar
• Eleftherianos I, Gökçen F, Felföldi G, et al.; ffrench-Constant RH, Reynolds SE. The immunoglobulin family protein Hemolin mediates cellular immune responses to bacteria in the insect Manduca sexta. Cell Microbiol. 2007;9:1137–1147.
   PubMed Web of Science ®Google Scholar
• Kumar P, Pandit SS, Baldwin IT. Tobacco Rattle Virus vector: A rapid and transient means of silencing Manduca sexta genes by plant mediated RNA interference. PLoS ONE. 2012;7:e31347–10.
   PubMed Web of Science ®Google Scholar
• Stoepler TM, Castillo JC, Lill JT, et al. A simple protocol for extracting hemocytes from wild caterpillars. JoVE. 2012;69:1–6.
   Google Scholar
• Kanost MR, Jiang H, Yu X-Q. Innate immune responses of a lepidopteran insect, Manduca sexta. Immunol Rev. 2004;198:97–105.
   PubMed Web of Science ®Google Scholar
• Blankenship JR, Heitman J. Calcineurin is required for Candida albicans to survive calcium stress in serum. Infect Immun. 2005;73:5767–5774.
   PubMed Web of Science ®Google Scholar
• Bruno VM. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Mol Microbiol. 2005;56:559–573.
   PubMed Web of Science ®Google Scholar
• Smith DA, Nicholls S, Morgan BA, et al. A conserved stress-activated protein kinase regulates a core stress response in the human pathogen Candida albicans. Mol Biol Cell. 2004;15:4179–4190.
   PubMed Web of Science ®Google Scholar
• Sniegowski P, Dombrowski P. Saccharomyces cerevisiae and Saccharomyces paradoxus coexist in a natural woodland site in North America and display different levels of reproductive isolation. FEMS Yeast Res. 2002;1:299–306.
   PubMedGoogle Scholar
• Pitt JI, Miller MW. Sporulation in Candida pulcherrima, Candida reukaufii and Chlamydozyma species: their relationships with Metschnikowia. Mycologia. 1968;60:663–685.
   Web of Science ®Google Scholar
• Dujon B, Sherman D, Fischer G, et al. Genome evolution in yeasts. Nature. 2004;430:35–44.
   PubMed Web of Science ®Google Scholar
• Ben-Ami R, Berman J, Novikov A, et al. Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel. Emerg Infect Dis. 2017;23:1–9.
   PubMed Web of Science ®Google Scholar
• Wong B, Perfect JR, Beggs S, et al. Production of the hexitol D-mannitol by Cryptococcus neoformans in vitro and in rabbits with experimental meningitis. Infect Immun. 1990;58:1664–1670.
   PubMed Web of Science ®Google Scholar
• Therneau TM, Grambsch PM. Modeling survival data: Extending the Cox model. Springer Science & Business Media New York; 2000.
   Google Scholar
• Kassambara A, Kosinski M, Biecek P, et al. survminer: drawing survival curves using ‘ggplot2ʹ. [accessed: 22 April 2020]. Available from: http://www.sthda.com/english/rpkgs/survminer/
   Google Scholar
• Wickham H. ggplot2. New York, NY: Springer-Verlag New York; 2009.
   Google Scholar
• Pinheiro J, Bates D, DebRoy S, et al. {nlme}: linear and nonlinear mixed effects models. [accessed 22 April 2020]. Available from: https://CRAN.R-project.org/package=nlme
   Google Scholar
• Kim D, Paggi JM, Park C, et al. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol. 2019;37:907–915.
   PubMed Web of Science ®Google Scholar
• Anders S, Pyl PT, Huber W. HTSeq–a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:166–169.
   PubMed Web of Science ®Google Scholar
• Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:21–31.
   Web of Science ®Google Scholar
• Varet H, Brillet-Guéguen L, Coppée J-Y, et al. SARTools: a DESeq2- and edger-based R pipeline for comprehensive differential analysis of RNA-seq data. PLoS ONE. 2016;11:e0157022–8.
   PubMed Web of Science ®Google Scholar
• Warnes GR, Bolker B, Bonebakker L, et al. gplots: various R programming tools for plotting data. [accessed 22 April 2020]. Available from: https://github.com/talgalili/gplots
   Google Scholar
• Camacho C, Coulouris G, Avagyan V, et al. BLAST+: architecture and applications. BMC Bioinformatics. 2009;10:421–429.
   PubMed Web of Science ®Google Scholar
• Liu Y, Shetty AC, Schwartz JA, et al. New signaling pathways govern the host response to C. albicans infection in various niches. Genome Res. 2015;25:679–689.
   PubMed Web of Science ®Google Scholar
• Conti HR, Bruno VM, Childs EE, et al. IL-17 receptor signaling in oral epithelial cells is critical for protection against oropharyngeal candidiasis. Cell Host Microbe. 2016;20:606–617.
   PubMed Web of Science ®Google Scholar
• Bruno VM, Shetty AC, Yano J, et al. Transcriptomic analysis of vulvovaginal candidiasis identifies a role for the NLRP3 inflammasome. mBio. 2015;6:3896.
   Web of Science ®Google Scholar
• Noble SM, Johnson AD. Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans. Eukaryot Cell. 2005;4:298–309.
   PubMedGoogle Scholar
• Alonso-Monge R, Navarro-García F, Molero G, et al. Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans. J Bacteriol. 1999;181:3058–3068.
   PubMed Web of Science ®Google Scholar
• Askew C, Sellam A, Epp E, et al. The zinc cluster transcription factor Ahr1p directs Mcm1p regulation of Candida albicans adhesion. Mol Microbiol. 2010;79:940–953.
   PubMed Web of Science ®Google Scholar
• Chiang LY, Sheppard DC, Bruno VM, et al. Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis. Cell Microbiol. 2007;9:233–245.
   PubMed Web of Science ®Google Scholar
• Vadkertiová R, Molnárová J, Vránová D, et al. Yeasts and yeast-like organisms associated with fruits and blossoms of different fruit trees. Can J Microbiol. 2012;58:1344–1352.
   PubMed Web of Science ®Google Scholar
• Li Y, Jiao P, Li Y, et al. The synergistic antifungal effect and potential mechanism of d-penicillamine combined with fluconazole against Candida albicans. Front Microbiol. 2019;10:2853.
   PubMed Web of Science ®Google Scholar
• Liu Y, Leung SSY, Guo Y, et al. The capsule depolymerase Dpo48 rescues Galleria mellonella and Mice from Acinetobacter baumannii systemic infections. Front Microbiol. 2019;10:545.
   PubMed Web of Science ®Google Scholar
• Wani FA, Amaduddin AB, Sheehan G, et al. Synthesis of novel benzimidazolium gemini surfactants and evaluation of their anti-Candida activity. ACS Omega. 2019;4:11871–11879.
   PubMed Web of Science ®Google Scholar
• Lu M, Yu C, Cui X, et al. Gentamicin synergises with azoles against drug-resistant Candida albicans. Int J Antimicrob Agents. 2018;51:107–114.
   PubMed Web of Science ®Google Scholar
• Sun L, Liao K, Wang D. Effects of magnolol and honokiol on adhesion, yeast-hyphal transition, and formation of biofilm by Candida albicans. PLoS ONE. 2015;10:e0117695–20.
   PubMed Web of Science ®Google Scholar
• Wurster S, Bandi A, Beyda ND, et al. Drosophila melanogaster as a model to study virulence and azole treatment of the emerging pathogen Candida auris. J Antimicrob Chemother. 2019;74:1904–1910.
   PubMed Web of Science ®Google Scholar
• Sun L, Zhi L, Shakoor S, et al. microRNAs involved in the control of innate immunity in Candida infected Caenorhabditis elegans. Nature. 2016;6:1–13.
   Google Scholar
• Cotter G, Doyle S, Kavanagh K. Development of an insect model for the in vivo pathogenicity testing of yeasts. FEMS Immunol Med Microbiol. 2000;27:163–169.
   PubMed Web of Science ®Google Scholar
• Kochi Y, Matsumoto Y, Sekimizu K, et al. Two-spotted cricket as an animal infection model of human pathogenic fungi. DD&T. 2017;11:259–266.
   Google Scholar
• Panpetch W, Somboonna N, Bulan DE, et al. Oral administration of live- or heat-killed Candida albicans worsened cecal ligation and puncture sepsis in a murine model possibly due to an increased serum (1→3)-β-D-glucan. PLoS ONE. 2017;12:e0181439–15.
   PubMed Web of Science ®Google Scholar
• Wellington M, Dolan K, Krysan DJ. Live Candida albicans suppresses production of reactive oxygen species in phagocytes. Infect Immun. 2008;77:405–413.
   PubMed Web of Science ®Google Scholar
• Means TK, Mylonakis E, Tampakakis E, et al. Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. J Exp Med. 2009;206:637–653.
   PubMed Web of Science ®Google Scholar
• Ma C, Kanost MR. A 1,3-glucan recognition protein from an insect, Manduca sexta, agglutinates microorganisms and activates the phenoloxidase cascade. J Biol Chem. 2000;275:7505–7514.
   PubMed Web of Science ®Google Scholar
• Rao X-J, Zhong X, Lin X-Y, et al. Characterization of a novel Manduca sexta beta-1, 3-glucan recognition protein (betaGRP3) with multiple functions. Insect Biochem Mol Biol. 2014;52:13–22.
   PubMed Web of Science ®Google Scholar
• Al Souhail Q, Hiromasa Y, Rahnamaeian M, et al. Characterization and regulation of expression of an antifungal peptide from hemolymph of an insect, Manduca sexta. Dev Comp Immunol. 2016;61:258–268.
   PubMed Web of Science ®Google Scholar