Sequential displacement of Type VI Secretion System effector genes leads to evolution of diverse immunity gene arrays in Vibrio cholerae

Abstract

Type VI secretion systems (T6SS) enable bacteria to engage neighboring cells in contact-dependent competition. In Vibrio cholerae, three chromosomal clusters each encode a pair of effector and immunity genes downstream of those encoding the T6SS structural machinery for effector delivery. Different combinations of effector-immunity proteins lead to competition between strains of V. cholerae, which are thought to be protected only from the toxicity of their own effectors. Screening of all publically available V. cholerae genomes showed that numerous strains possess long arrays of orphan immunity genes encoded in the 3′ region of their T6SS clusters. Phylogenetic analysis reveals that these genes are highly similar to those found in the effector-immunity pairs of other strains, indicating acquisition by horizontal gene transfer. Extensive genomic comparisons also suggest that successive addition of effector-immunity gene pairs replaces ancestral effectors, yet retains the cognate immunity genes. The retention of old immunity genes perhaps provides protection against nearby kin bacteria in which the old effector was not replaced. This mechanism, combined with frequent homologous recombination, is likely responsible for the high diversity of T6SS effector-immunity gene profiles observed for V. cholerae and closely related species.

Analysis of Vibrio cholerae genomes using a novel bioinformatic tool identifies new, active Type VI Secretion System gene clusters

“…Thomas et al have previously shown experimentally that different effectors within V. cholerae auxiliary clusters can be swapped among strains (51). Kirchberger et al have also proposed that effector modules and tap genes can be swapped and acquired (52). However, to our knowledge, this study is the first to experimentally show that an additional non-native T6SS auxiliary cluster can be acquired and used by a V. cholerae strain to kill kin cells lacking the immunity protein.…”

Causalities of war: The connection between type VI secretion system and microbiota

“…T6SS armament can be increased by acquisition of individual effector modules, or small operons encoding vgrG/hcp/paar and cognate effector modules or in the case of Bacteroidetes via horizontally acquired entire T6SS operons on integrative conjugative elements with near 100% identity amongst Bacteroides species Coyne, Zitomersky, McGuire, Earl, & Comstock, 2014;Unterweger et al, 2014). Maintaining ancestral immunity genes or acquiring immunity but not effector genes is a good strategy to cope with T6SS-active strains in a population at lower cost, such as the C-type immunity gene in the aux-1 cluster of V. cholerae or the recently described acquired interbacterial defence gene clusters, which encode arrays of immunity genes (Alteri et al, 2017;Kirchberger et al, 2017;Ross et al, 2019;Wexler et al, 2016).…”

“…Opposing strain swarms of Proteus mirabilis form T6SS-dependent "battle lines" of segregation called Dienes lines (Alteri et al, 2017). In Vibrio cholerae, related families of effectors (>30% identity) are associated with immunity proteins whose variation is far greater (Kirchberger, Unterweger, Provenzano, Pukatzki, & Boucher, 2017;Unterweger et al, 2014). Combinations of distinct effector modules within a strain further contribute to interstrain incompatibility and confer a significant competitive advantage over rivals (Unterweger et al, 2014).…”

“…This enables coordinated killing of prey and DNA acquisition from lysed bacteria, which fosters horizontal gene transfer. Incorporation of this genetic material enables the acquisition of new antimicrobial resistance genes, pathogenicity islands, or T6SS effectors/immunity pairs, all of which could provide an evolutionary advantage (Blokesch, 2017;Borgeaud et al, 2015;Kirchberger et al, 2017;Thomas, Watve, Ratcliff, & Hammer, 2017).…”

Acquired interbacterial defense systems protect against interspecies antagonism in the human gut microbiome

“…Mounting evidence suggests that competitive interactions between bacteria predominate in many environments (23). This evolutionary pressure has undoubtedly led to the wide dissemination of idiosyncratically orphaned immunity genes predicted to provide resistance to diverse antagonistic pathways (21,(24)(25)(26)(27). Modeling studies predict that interbacterial antagonism is a critical contributor to the maintenance of a stable gut community (28).…”