Commensal pathogen competition impacts host viability

Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7099-7104. doi: 10.1073/pnas.1802165115. Epub 2018 Jun 18.

Abstract

While the structure and regulatory networks that govern type-six secretion system (T6SS) activity of Vibrio cholerae are becoming increasingly clear, we know less about the role of T6SS in disease. Under laboratory conditions, V. cholerae uses T6SS to outcompete many Gram-negative species, including other V. cholerae strains and human commensal bacteria. However, the role of these interactions has not been resolved in an in vivo setting. We used the Drosophila melanogaster model of cholera to define the contribution of T6SS to V. cholerae pathogenesis. Here, we demonstrate that interactions between T6SS and host commensals impact pathogenesis. Inactivation of T6SS, or removal of commensal bacteria, attenuates disease severity. Reintroduction of the commensal, Acetobacter pasteurianus, into a germ-free host is sufficient to restore T6SS-dependent pathogenesis in which T6SS and host immune responses regulate viability. Together, our data demonstrate that T6SS acts on commensal bacteria to promote the pathogenesis of V. cholerae.

Keywords: Drosophila; T6SS; Vibrio cholerae; microbiome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetobacter / genetics
  • Acetobacter / metabolism*
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cholera / genetics
  • Cholera / metabolism*
  • Cholera / microbiology
  • Disease Models, Animal
  • Drosophila melanogaster
  • Type VI Secretion Systems / genetics
  • Type VI Secretion Systems / metabolism*
  • Vibrio cholerae / genetics
  • Vibrio cholerae / metabolism*

Substances

  • Bacterial Proteins
  • Type VI Secretion Systems