Salmonella Typhimurium utilizes a T6SS mediated antibacterial weapon to establish in the host gut
Significance Gram negative bacteria use the type VI secretion system (T6SS) to deliver effectors into adjacent cells. Salmonella Typhimurium is an enteric pathogen that causes disease in millions of individuals each year. Its ability to infect the mammalian gut is a key factor that contributes to its virulence and transmission to new hosts. However, many of the details on how Salmonella successfully colonizes the gut and persists among members of the gut microbiota remain to be deciphered. In this work, we provide evidence that Salmonella uses an antibacterial weapon, the type VI secretion system, to establish infection in the gut. In addition, our results suggest that S. Typhimurium selectively targets specific members of the microbiota to invade the gastrointestinal tract. 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.
Proceedings of the National Academy of Sciences