
Full text loading...
Category: Bacterial Pathogenesis
Type VI Secretion Systems and the Gut Microbiota, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781683670285/9781683670278_Chap27-1.gif /docserver/preview/fulltext/10.1128/9781683670285/9781683670278_Chap27-2.gifAbstract:
Type VI secretion systems (T6SSs) were first identified and characterized for pathogenic bacteria of the proteobacterial phylum ( 1 , 2 ). The discovery in 2010 that these secretion systems can target and intoxicate not only eukaryotic cells but also other bacteria ( 3 ) revealed that some T6SSs help bacteria compete with other bacteria in a community setting. Indeed, many proteobacterial symbionts, including the plant symbiont Pseudomonas putida, the bumble bee gut symbiont Snodgrassella alvi, and the squid symbiont Vibrio fischeri, all have T6SSs that provide a competitive advantage in their natural ecosystems ( 4 – 6 ). An early in silico analysis using clusters of orthologous groups (COGs) models of proteobacterial T6SS proteins against primary sequence databases suggested that T6SSs are largely confined to proteobacterial species, which are minor members of some human-associated microbial communities such as the gut microbiota ( 7 , 8 )
Full text loading...
(A) Open reading frame (ORF) maps of one representative locus of each of the three genetic architectures (GA) of T6SS loci of gut Bacteroidales. T6SS loci of GA1 and GA2 are present in diverse Bacteroidales species, whereas GA3 T6SS loci are confined to B. fragilis. T6SS loci of a given GA are extremely similar to each other except for the divergent regions noted by lines above the genes, which encode known or putative effector and immunity proteins. The major TssD protein of GA3 is noted, as is the TssD protein of the GA2 loci that have C-terminal extensions likely conferring toxin activity. The ends of the GA1 and GA2 loci have not been precisely determined. (B) ORF maps of ICE containing GA1 and GA2 T6SS loci of two Bacteroides species. The T6SS loci are designated by a line above the map. Genes involved in conjugative transfer (tra genes) are colored green ( 15 ). (C) The abundant fecal gut Bacteroidales from three different healthy humans (CL02, CL09, and CL03) were analyzed for the presence of T6SSs. Seven Bacteroidales species were isolated and sequenced from subject CL02 and from subject CL09. Four of the seven species harbor nearly identical GA1 T6SSs loci within a subject, demonstrating transfer of these ICE between these strains in their gut ( 12 , 15 ). In contrast, of the eight species isolated and sequenced from human subject CL03, two contain GA2 T6SS loci, albeit with different divergent regions. Therefore, these GA2 ICE were not transferred between these species. In addition, one species contains a GA1 T6SS locus and the B. fragilis strain from this individual contains a GA3 T6SS locus ( 15 ). Red, green, and yellow dots represent the GA1, GA2, and GA3 T6SS loci.
T6SS-mediated antagonism in the mammalian gut. (A) Three different proteobacterial enteric pathogens, Vibrio cholerae, Salmonella enterica Typhimurium, and Shigella sonnei, use T6SSs to target resident gut E. coli to overcome colonization resistance and cause disease in animal models ( 32 – 36 ). In the case of V. cholerae, the lysed E. coli organisms initiate innate immune responses that upregulate virulence factors and increase dissemination ( 32 ). (B) Bacteroides fragilis GA3 T6SS antagonize nearly all gut Bacteroidales species in vitro. In vivo, strong antagonistic effects are seen between two distinct B. fragilis strains likely due to their localization at the mucosal surface, where they will make frequent contacts. This intraspecies antagonism may lead to the dominance of one strain. B. vulgatus was also significantly antagonized by a B. fragilis GA3 T6SS, possibly due to overlapping nutritional niches. In contrast, a significant antagonistic effect by the GA3 T6SS of B. fragilis was not observed when this organism was coinoculated with B. thetaiotaomicron. These varied effects may be due to the substrate preferences of these species, which may spatially segregate them under normal dietary conditions.