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

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

Author information

1
Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305;
2
Laboratoire d'Ingénierie des Systèmes Macromoléculaires (UMR7255), Institut de Microbiologie de la Méditerranée, Aix-Marseille Université - CNRS, 13402 Marseille, France;
3
Division of Oncology, Department of Medicine and Pathology, Stanford School of Medicine, Stanford University, Stanford, CA 94305.
4
Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305; dmonack@stanford.edu.

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

PMID:
27503894
PMCID:
PMC5003274
DOI:
10.1073/pnas.1608858113
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

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