Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut

Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):E5044-51. doi: 10.1073/pnas.1608858113. Epub 2016 Aug 8.

Abstract

The mammalian gastrointestinal tract is colonized by a high-density polymicrobial community where bacteria compete for niches and resources. One key competition strategy includes cell contact-dependent mechanisms of interbacterial antagonism, such as the type VI secretion system (T6SS), a multiprotein needle-like apparatus that injects effector proteins into prokaryotic and/or eukaryotic target cells. However, the contribution of T6SS antibacterial activity during pathogen invasion of the gut has not been demonstrated. We report that successful establishment in the gut by the enteropathogenic bacterium Salmonella enterica serovar Typhimurium requires a T6SS encoded within Salmonella pathogenicity island-6 (SPI-6). In an in vitro setting, we demonstrate that bile salts increase SPI-6 antibacterial activity and that S Typhimurium kills commensal bacteria in a T6SS-dependent manner. Furthermore, we provide evidence that one of the two T6SS nanotube subunits, Hcp1, is required for killing Klebsiella oxytoca in vitro and that this activity is mediated by the specific interaction of Hcp1 with the antibacterial amidase Tae4. Finally, we show that K. oxytoca is killed in the host gut in an Hcp1-dependent manner and that the T6SS antibacterial activity is essential for Salmonella to establish infection within the host gut. Our findings provide an example of pathogen T6SS-dependent killing of commensal bacteria as a mechanism to successfully colonize the host gut.

Keywords: Salmonella Typhimurium; T6SS SPI-6; antiprokaryotic activity; colonization; gut microbiota.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiosis*
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / toxicity*
  • Bile Acids and Salts / pharmacology
  • Culture Media / chemistry
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Tract / microbiology
  • Gastrointestinal Tract / pathology
  • Genomic Islands
  • Klebsiella oxytoca / drug effects
  • Klebsiella oxytoca / growth & development
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Salmonella Infections, Animal / microbiology*
  • Salmonella Infections, Animal / pathology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / pathogenicity*
  • Type VI Secretion Systems / genetics*
  • Type VI Secretion Systems / metabolism
  • Virulence Factors / biosynthesis
  • Virulence Factors / genetics
  • Virulence Factors / toxicity*

Substances

  • Bacterial Proteins
  • Bile Acids and Salts
  • Culture Media
  • Type VI Secretion Systems
  • Virulence Factors