title: Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish in the host gut.
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.
authors: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305;
authors: Thibault G
authors: 0000-0003-0723-6924
authors: TG
authors: Sana
authors: Laboratoire d'Ingénierie des Systèmes Macromoléculaires (UMR7255), Institut de Microbiologie de la Méditerranée, Aix-Marseille Université - CNRS, 13402 Marseille, France;
authors: Nicolas
authors: N
authors: Flaugnatti
authors: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305;
authors: Kyler A
authors: KA
authors: Lugo
authors: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305;
authors: Lilian H
authors: LH
authors: Lam
authors: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305;
authors: Amanda
authors: A
authors: Jacobson
authors: Division of Oncology, Department of Medicine and Pathology, Stanford School of Medicine, Stanford University, Stanford, CA 94305.
authors: Virginie
authors: V
authors: Baylot
authors: Laboratoire d'Ingénierie des Systèmes Macromoléculaires (UMR7255), Institut de Microbiologie de la Méditerranée, Aix-Marseille Université - CNRS, 13402 Marseille, France;
authors: Eric
authors: E
authors: Durand
authors: Laboratoire d'Ingénierie des Systèmes Macromoléculaires (UMR7255), Institut de Microbiologie de la Méditerranée, Aix-Marseille Université - CNRS, 13402 Marseille, France;
authors: Laure
authors: L
authors: Journet
authors: Laboratoire d'Ingénierie des Systèmes Macromoléculaires (UMR7255), Institut de Microbiologie de la Méditerranée, Aix-Marseille Université - CNRS, 13402 Marseille, France;
authors: Eric
authors: E
authors: Cascales
authors: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305; dmonack@stanford.edu.
authors: Denise M
authors: DM
authors: Monack
mesh_terms: D000818:Animals; D000898:Antibiosis; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000633:toxicity*; D001647:Bile Acids and Salts / Q000494:pharmacology; D003470:Culture Media / Q000737:chemistry; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000382:microbiology / Q000473:pathology; D044404:Genomic Islands; D041121:Klebsiella oxytoca / Q000187:drug effects / Q000254:growth & development; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000382:microbiology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D000069376:Type VI Secretion Systems / Q000235:genetics* / Q000378:metabolism; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics / Q000633:toxicity*
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D003470:Culture Media; D000069376:Type VI Secretion Systems; D037521:Virulence Factors
keywords: Salmonella Typhimurium; T6SS SPI-6; antiprokaryotic activity; colonization; gut microbiota