T6SS and ExoA of flesh-eating Aeromonas hydrophila in peritonitis and necrotizing fasciitis during mono- And polymicrobial infections

Ana Fernández-Bravo, Paul B. Kilgore, Jourdan A. Andersson, Elizabeth Blears, Maria José Figueras, Nur A. Hasan, Rita R. Colwell, Jian Sha, Ashok K. Chopra

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

An earlier report described a human case of necrotizing fasciitis (NF) caused by mixed infection with 4 Aeromonas hydrophila strains (NF1–NF4). While the NF2, NF3, and NF4 strains were clonal and possessed exotoxin A (ExoA), the NF1 strain was determined to be phylogenetically distinct, harboring a unique type 6 secretion system (T6SS) effector (TseC). During NF1 and NF2 mixed infection, only NF1 disseminated, while NF2 was rapidly killed by a contact-dependent mechanism and macrophage phagocytosis, as was demonstrated by using in vitro models. To confirm these findings, we developed 2 NF1 mutants (NF1ΔtseC and NF1ΔvasK); vasK encodes an essential T6SS structural component. NF1 VasK and TseC were proven to be involved in contact-dependent killing of NF2 in vitro, as well as in its elimination at the intramuscular injection site in vivo during mixed infection, with overall reduced mouse mortality. ExoA was shown to have an important role in NF by both NF1-exoA (with cis exoA) and NF2 during monomicrobial infection. However, the contribution of ExoA was more important for NF2 than NF1 in the murine peritonitis model. The NF2ΔexoA mutant did not significantly alter animal mortality or NF1 dissemination during mixed infection in the NF model, suggesting that the ExoA activity was significant at the injection site. Immunization of mice to ExoA protected animals from NF2 monomicrobial challenge, but not from polymicrobial infection because of NF2 clearance. This study clarified the roles of T6SS and ExoA in pathogenesis caused by A. hydrophila NF strains in both mouse peritonitis and NF models in monomicrobial and polymicrobial infections.

Original languageEnglish (US)
Pages (from-to)24084-24092
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number48
DOIs
StatePublished - Nov 26 2019

Keywords

  • Animal models
  • ExoA
  • Mono- and polymicrobial Aeromonas hydrophila infections
  • Necrotizing fasciitis
  • T6SS

ASJC Scopus subject areas

  • General

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