Type VI Secretion Systems and the Gut Microbiota

The human colonic microbiota is a dense ecosystem comprised of numerous microbes, including bacteria, phage, fungi, archaea, and protozoa, that compete for nutrients and space. Studies are beginning to reveal the antagonistic mechanisms that gut bacteria use to compete with other members of this ecosystem. In the healthy human colon, the majority of the Gram-negative bacteria are of the order Bacteroidales. Proteobacteria, such as Escherichia coli, are numerically fewer but confer important properties to the host, such as colonization resistance. Several enteric pathogens use type VI secretion systems (T6SSs) to antagonize symbiotic gut E. coli, facilitating colonization and disease progression. T6SS loci are also widely distributed in human gut Bacteroidales, which includes three predominant genera: Bacteroides, Parabacteroides, and Prevotella. There are three distinct genetic architectures of T6SS loci among the gut Bacteroidales, termed GA1, GA2, and GA3. GA1 and GA2 T6SS loci are contained on integrative and conjugative elements and are the first T6SS loci shown to be readily transferred in the human gut between numerous species and families of Bacteroidales. In contrast, the GA3 T6SSs are present exclusively in Bacteroides fragilis. There are divergent regions in all three T6SS GAs that contain genes encoding effector and immunity proteins, many of which function by unknown mechanisms. To date, only the GA3 T6SSs have been shown to antagonize bacteria, and they target nearly all gut Bacteroidales species analyzed. This review delves more deeply into properties of the T6SSs of these human gut bacteria and the ecological outcomes of their synthesis in vivo.