Many of the same pathogenesis traits are required for virulence in both mammals and non-vertebrate hosts. Taken in their totality, our results indicate that a common, fundamental set of molecular mechanisms is employed by pathogens against a widely divergent array of metazoan hosts. As part of our efforts, we have implemented a variety of invertebrate and mammalian models to demonstrated that:

  1. There are extensive similarities between infections in mammals and non-vertebrate models, including nematode and insect hosts,
  2. The model microscopic nematode C. elegans grown on non-pathogenic yeasts has a life span similar to, or longer than, nematodes fed on the usual laboratory food source, but human pathogens kill C. elegans,
  3. A number of virulence traits that are involved in mammalian infection from a variety of pathogens are associated with C. elegans disease,
  4. C. elegans assays can be used to identify novel virulence factors that are associated with mammalian infection, and these virulence factors provide important insights into bacterial and fungal biology,
  5. C. elegans assays can be used to identify and study compounds with antimicrobial efficacy and multidrug resistance (MDR) mechanisms,
  6. During polymicrobial infection, prokaryote-eukaryote interactions modulate microbial virulence, and,
  7. There are evolutionarily conserved pathways for the innate sensing of pathogens and we identified C. elegans receptors that (similar to their mammalian orthologues) mediate host defense.

Select Publications

a) Means TK, Mylonakis E, Tampakakis E, Colvin RA, Seung E, Puckett L, Tai MF, Stewart CR, Pukkila-Worley R, Hickman SE, Moore KJ, Calderwood SB, Hacohen N, Luster AD, El-Khoury J. Evolutionary-conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. J Exp Med. 2009;206(3):637-53. PMID: 19237602 PMCID: PMC2699123

b) Peleg AY, Tampakakis E, Fuchs BB, Eliopoulos GM, Moellering RC Jr, Mylonakis E. Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans. Proc Natl Acad Sci USA. 2008;105(38):14585-90. PMID: 18794525 PMCID: PMC2567192

c) Rajamuthiah R, Jayamani E, Majed H, Conery AL, Kim W, Kwon B, Fuchs BB, Kelso MJ, Ausubel FM, Mylonakis E. Antibacterial properties of 3-(phenylsulfonyl)-2-pyrazinecarbonitrile. Bioorg Med Chem Lett. 2015 Nov 15;25(22):5203-7. PMID: 26459212. PMCID: PMC4718707

d) Arvanitis M, Li G, Li DD, Cotnoir D, Ganley-Leal L, Carney DW, Sello JK, Mylonakis E. A Conformationally constrained cyclic acyldepsipeptide is highly effective in mice infected with methicillin-susceptible and -resistant Staphylococcus aureus. PLoS One. 2016 Apr 21;11(4):e0153912. PMID: 27101010. PMCID: PMC48395603