title: Cross-talk among flesh-eating Aeromonas hydrophila strains in mixed infection leading to necrotizing fasciitis.
abstract: Necrotizing fasciitis (NF) caused by flesh-eating bacteria is associated with high case fatality. In an earlier study, we reported infection of an immunocompetent individual with multiple strains of Aeromonas hydrophila (NF1-NF4), the latter three constituted a clonal group whereas NF1 was phylogenetically distinct. To understand the complex interactions of these strains in NF pathophysiology, a mouse model was used, whereby either single or mixed A. hydrophila strains were injected intramuscularly. NF2, which harbors exotoxin A (exoA) gene, was highly virulent when injected alone, but its virulence was attenuated in the presence of NF1 (exoA-minus). NF1 alone, although not lethal to animals, became highly virulent when combined with NF2, its virulence augmented by cis-exoA expression when injected alone in mice. Based on metagenomics and microbiological analyses, it was found that, in mixed infection, NF1 selectively disseminated to mouse peripheral organs, whereas the other strains (NF2, NF3, and NF4) were confined to the injection site and eventually cleared. In vitro studies showed NF2 to be more effectively phagocytized and killed by macrophages than NF1. NF1 inhibited growth of NF2 on solid media, but ExoA of NF2 augmented virulence of NF1 and the presence of NF1 facilitated clearance of NF2 from animals either by enhanced priming of host immune system or direct killing via a contact-dependent mechanism.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Ponnusamy
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kozlova
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Jian
authors.initials: J
authors.lastname: Sha
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Tatiana E
authors.initials: TE
authors.lastname: Erova
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Sasha R
authors.initials: SR
authors.lastname: Azar
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Eric C
authors.initials: EC
authors.lastname: Fitts
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Kirtley
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Tiner
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Jourdan A
authors.initials: JA
authors.lastname: Andersson
authors.affiliation: Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, Food and Drug Administration, Laurel, MD 20708;
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Grim
authors.affiliation: CosmosID Inc., Rockville, MD 20850;
authors.forename: Richard P
authors.initials: RP
authors.lastname: Isom
authors.affiliation: CosmosID Inc., Rockville, MD 20850; Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies, University of Maryland, College Park, MD 20742;
authors.forename: Nur A
authors.initials: NA
authors.lastname: Hasan
authors.affiliation: CosmosID Inc., Rockville, MD 20850; Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies, University of Maryland, College Park, MD 20742; Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205 rcolwell@umiacs.umd.edu achopra@utmb.edu.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Colwell
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555; rcolwell@umiacs.umd.edu achopra@utmb.edu.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chopra
mesh_terms: D016980:Aeromonas hydrophila / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D000818:Animals; D060085:Coinfection / Q000382:microbiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D019115:Fasciitis, Necrotizing / Q000382:microbiology* / Q000473:pathology; D005798:Genes, Bacterial; D007267:Injections; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009068:Movement; D009928:Organ Specificity; D010587:Phagocytosis; D000067996:RAW 264.7 Cells; D016019:Survival Analysis; D014774:Virulence
keywords: Aeromonas hydrophila; intramuscular mouse model; metagenomics; mixed infections; necrotizing fasciitis