Pandemic Vibrio cholerae shuts down site-specific recombination to retain an interbacterial defence mechanism

Santoriello, Francis J.; Michel, Lina; Unterweger, Daniel; Pukatzki, Stefan

doi:10.1038/s41467-020-20012-7

Cited by 19 publications

(13 citation statements)

References 78 publications

(114 reference statements)

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“…In other bacterial lineages, T6SS loci are typically contained on non-core genomic islands, but, with few exceptions [ 8 ], are rarely found on conjugative elements. Some T6SS-associated genes, such as immunity genes [ 9 ], reside on mobile elements, and a full T6SS locus is present on a mobile prophage-like element in environmental Vibrio cholerae strains [ 10 ]. The presence of complete Bacteroidales T6SS loci on ICE allows for their distribution to other co-resident Bacteroidales species in the human gut.…”

Section: Introductionmentioning

confidence: 99%

Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering

2021

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The human gut microbiota is a dense microbial ecosystem with extensive opportunities for bacterial contact-dependent processes such as conjugation and Type VI secretion system (T6SS)-dependent antagonism. In the gut Bacteroidales, two distinct genetic architectures of T6SS loci, GA1 and GA2, are contained on Integrative and Conjugative Elements (ICE). Despite intense interest in the T6SSs of the gut Bacteroidales, there is only a superficial understanding of their evolutionary patterns, and of their dissemination among Bacteroidales species in human gut communities. Here, we combine extensive genomic and metagenomic analyses to better understand their ecological and evolutionary dynamics. We identify new genetic subtypes, document extensive intrapersonal transfer of these ICE to Bacteroidales species within human gut microbiomes, and most importantly, reveal frequent population fixation of these newly armed strains in multiple species within a person. We further show the distribution of each of the distinct T6SSs in human populations and show there is geographical clustering. We reveal that the GA1 T6SS ICE integrates at a minimal recombination site leading to their integration throughout genomes and their frequent interruption of genes, whereas the GA2 T6SS ICE integrate at one of three different tRNA genes. The exclusion of concurrent GA1 and GA2 T6SSs in individual strains is associated with intact T6SS loci and with an ICE-encoded gene. By performing a comprehensive analysis of mobile genetic elements (MGE) in co-resident Bacteroidales species in numerous human gut communities, we identify 74 MGE that transferred to multiple Bacteroidales species within individual gut microbiomes. We further show that only three other MGE demonstrate multi-species spread in human gut microbiomes to the degree demonstrated by the GA1 and GA2 ICE. These data underscore the ubiquity and dissemination of mobile T6SS loci within Bacteroidales communities and across human populations.

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Section: Introductionmentioning

confidence: 99%

Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering

2021

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“…This degree of variation in E-I profiles is mainly attributable to horizontal gene transfer (HGT) ( Kirchberger et al, 2017 ), which, in V. cholerae , is tightly linked with T6SS activity ( Borgeaud et al, 2015 ; Thomas et al, 2017 ; Matthey et al, 2019 ). The acquisition and replacement of effector and/or immunity genes is orchestrated through various recombination mechanisms, namely, homologous recombination and homology-facilitated illegitimate recombination for polymorphic loci ( Cooper et al, 2017 ; Kirchberger et al, 2017 ; Thomas et al, 2017 ) and site-specific recombination in the case of monomorphic loci ( Miyata et al, 2013a ; Labbate et al, 2016 ; Santoriello et al, 2020 ). Ancestral immunity genes can be entirely replaced or retained with the addition of new E-I modules within a locus ( Kirchberger et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Modular Molecular Weaponry Plays a Key Role in Competition Within an Environmental Vibrio cholerae Population

et al. 2021

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The type VI secretion system (T6SS) operons of Vibrio cholerae contain extraordinarily diverse arrays of toxic effector and cognate immunity genes, which are thought to play an important role in the environmental lifestyle and adaptation of this human pathogen. Through the T6SS, proteinaceous “spears” tipped with antibacterial effectors are injected into adjacent cells, killing those not possessing immunity proteins to these effectors. Here, we investigate the T6SS-mediated dynamics of bacterial competition within a single environmental population of V. cholerae. We show that numerous members of a North American V. cholerae population possess strain-specific repertoires of cytotoxic T6SS effector and immunity genes. Using pairwise competition assays, we demonstrate that the vast majority of T6SS-mediated duels end in stalemates between strains with different T6SS repertoires. However, horizontally acquired effector and immunity genes can significantly alter the outcome of these competitions. Frequently observed horizontal gene transfer events can both increase or reduce competition between distantly related strains by homogenizing or diversifying the T6SS repertoire. Our results also suggest temperature-dependent outcomes in T6SS competition, with environmental isolates faring better against a pathogenic strain under native conditions than under those resembling a host-associated environment. Taken altogether, these interactions produce density-dependent fitness effects and a constant T6SS-mediated arms race in individual V. cholerae populations, which could ultimately preserve intraspecies diversity. Since T6SSs are widespread, we expect within-population diversity in T6SS repertoires and the resulting competitive dynamics to be a common theme in bacterial species harboring this machinery.

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“…3). Finally, the Aux3 effector/immunity pair (tseH/tsiH), which is enriched in pandemic V. cholerae strains [36], is restricted to Vch, Vmim, and the Vang clade. It is important to note, that our analysis is restricted by the small number of available Vflu and Vfur genomes.…”

Section: Cross-species Effector Gene Distribution Indicates the Presence Of Pandemic-associatedmentioning

confidence: 99%

“…Aux3 minimally encodes an effector-immunity pair (tseH-tsiH) and a PAAR adaptor necessary for its loading onto the T6SS [35], while Aux4, Aux5, and Aux6 encode their own Hcp, VgrG, and chaperone along with effector-immunity pairs. Aux3 and Aux4 are both carried on mobile genetic elements and are transferred between strains [32,36]. The V. cholerae species is a diverse collection of strains that display varying degrees of virulence to humans, including harmless strains, opportunistic pathogens, and pathogenic strains that have evolved to infect the human gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

PandemicVibrio choleraeAcquired Competitive Traits from an EnvironmentalVibrioSpecies

Santoriello

Boucher

et al. 2021

Preprint

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Background: Vibrio cholerae, the causative agent of cholera, is a human pathogen that thrives in estuarine environments. V. cholerae competes with neighboring microbes by the contact-dependent translocation of toxic effectors with the type VI secretion system (T6SS). Effector types are highly variable across V. cholerae strains, but all pandemic isolates encode the same set of distinct effectors. It is possible that acquisition of these effectors via horizontal gene transfer played a role in the development of pandemic V. cholerae. Results: We assessed the distribution of V. cholerae T6SS loci across multiple Vibrio species. We showed that the fish-pathogen V. anguillarum encodes all three V. cholerae core loci as well as two of the four additional auxiliary clusters. We further demonstrated that V. anguillarum shares T6SS effectors with V. cholerae, including every pandemic-associated V. cholerae effector. We identified a novel T6SS cluster (Accessory Aux1) that is widespread in V. anguillarum and encodes the pandemic V. cholerae effector TseL. We highlighted potential gene transfer events of Accessory Aux1 from V. anguillarum to V. cholerae. Finally, we showed that TseL from V. cholerae can be neutralized by the V. anguillarum Accessory Aux1 immunity protein and vice versa, indicating V. anguillarum as the donor of tseL to the V. cholerae species. Conclusions: V. anguillarum constitutes an environmental reservoir of pandemic-associated V. cholerae T6SS effectors. V. anguillarum and V. cholerae likely share an environmental niche, compete, and exchange T6SS effectors. Further, our findings highlight the fish as a potential reservoir of pandemic V. cholerae.

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Pandemic Vibrio cholerae shuts down site-specific recombination to retain an interbacterial defence mechanism

Cited by 19 publications

References 78 publications

Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering

Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering

Modular Molecular Weaponry Plays a Key Role in Competition Within an Environmental Vibrio cholerae Population

PandemicVibrio choleraeAcquired Competitive Traits from an EnvironmentalVibrioSpecies

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