Cross-talk among flesh-eating Aeromonas hydrophila strains in mixed infection leading to necrotizing fasciitis

Duraisamy Ponnusamy, Elena V. Kozlova, Jian Sha, Tatiana E. Erova, Sasha R. Azar, Eric C. Fitts, Michelle L. Kirtley, Bethany L. Tiner, Jourdan A. Andersson, Christopher J. Grim, Richard P. Isom, Nur A. Hasan, Rita R. Colwell, Ashok K. Chopra

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)722-727
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number3
DOIs
StatePublished - Jan 19 2016

Keywords

  • Aeromonas hydrophila
  • Intramuscular mouse model
  • Metagenomics
  • Mixed infections
  • Necrotizing fasciitis

ASJC Scopus subject areas

  • General

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    Ponnusamy, D., Kozlova, E. V., Sha, J., Erova, T. E., Azar, S. R., Fitts, E. C., Kirtley, M. L., Tiner, B. L., Andersson, J. A., Grim, C. J., Isom, R. P., Hasan, N. A., Colwell, R. R., & Chopra, A. K. (2016). Cross-talk among flesh-eating Aeromonas hydrophila strains in mixed infection leading to necrotizing fasciitis. Proceedings of the National Academy of Sciences of the United States of America, 113(3), 722-727. https://doi.org/10.1073/pnas.1523817113