Activity, delivery, and diversity of Type VI secretion effectors

Jurėnas, Dukas; Journet, Laure

doi:10.1111/mmi.14648

Cited by 103 publications

(120 citation statements)

References 119 publications

(299 reference statements)

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“…VgrG and PAAR are found in large numbers in both orphan and main operons, suggesting no bias (Figure 4B). Since T6Es act generally as antibacterial toxins (Jurėnas and Journet 2021), the identity of the C-terminal domains of "evolved" T6SS cores are of high interest to science and industry. We surveyed all pfam domains encoded in C-terminal domains of HCP, VgrG, and PAAR.…”

Section: T6ss-encoding Bacteria Live a Pathogenic Lifestyle And Are Enriched In Specific Tissues Of Humans And Plantsmentioning

confidence: 99%

Large-scale discovery of candidate type VI secretion effectors with antibacterial activity

Geller

Zlotkin

Levy

2021

Preprint

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Type VI secretion systems (T6SS) are common bacterial contractile injection systems that inject toxic effector proteins into neighboring cells. Effector discovery is generally done manually, and computational approaches used for effector discovery depend on genetic linkage to T6SS genes and/or sequence similarity to known effectors. We bioinformatically investigated T6SS in more than 11,832 genomes of Gram negative bacteria. We found that T6SS encoding bacteria are host-associated and pathogenic, enriched in specific human and plant tissues, while depleted in marine, soil, and engineered environments. Analysis of T6SS cores with C-terminal domains ("evolved" cores) showed "evolved" HCP are rare, overwhelmingly encoded in orphan operons, and are largely restricted to Escherichia. Using the wealth of data generated from our bioinformatic analysis, we developed two algorithms for large-scale discovery of T6SS effector proteins (T6Es). We experimentally validated ten putative antibacterial T6SS effector proteins and one cognate immunity gene from a diverse species. This study provides a systematic genomic perspective of the role of the T6SS in nature, a thorough analysis of T6E evolution and genomic properties, and discovery of a large number of candidate T6Es using new approaches.

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Section: T6ss-encoding Bacteria Live a Pathogenic Lifestyle And Are Enriched In Specific Tissues Of Humans And Plantsmentioning

confidence: 99%

Large-scale discovery of candidate type VI secretion effectors with antibacterial activity

Geller

Zlotkin

Levy

2021

Preprint

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“…Using the fully resolved organismal phylogeny as a framework, next we examined the molecular evolution of their T6SS genes. The T6SS is a phage tail-like contractile nanomachine for injecting effectors (i.e., toxins) into eukaryotic or bacterial cells, and plays a major role in pathogenesis, symbiosis, or interbacterial competition (33,34). For A. tumefaciens, the T6SS is a key weapon for in planta competition between different genomospecies (27) and against other bacteria (30).…”

Section: The Type VI Secretion System (T6ss) Genesmentioning

confidence: 99%

“…We first focus on genes encoding the T6SS, a phage tail-like contractile nanomachine commonly found in Proteobacteria and used to inject effectors into eukaryotic or bacterial cells. The T6SS has major roles in pathogenesis, symbiosis, and interbacterial competition [30][31][32][33]. For A. tumefaciens, the T6SS is a key weapon for in planta competition between different genomospecies [7] and against other bacteria [27].…”

Section: Diversity and Evolution Of The T6ss Genesmentioning

confidence: 99%

Modular evolution of secretion systems and virulence plasmids in a bacterial species complex

Chou

Haryono

et al. 2021

Preprint

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Many pathogenic bacteria are recognized as species complexes and uncertainties regarding the organization of their genetic diversity are challenges for research efforts. Within Agrobacterium tumefaciens, multiple genomospecies have been identified; however, the exact species boundaries are unclear, which causes chaos in nomenclature and hampers communication. In this work, we conducted targeted genome sequencing to achieve a comprehensive and balanced taxon sampling within this complex. Our results from genome-wide sequence identity, core genome phylogeny, and gene content not only supported that those recognized genomospecies are distinct biological entities but also identified novel genomospecies. Based on the fully resolved phylogeny, we further investigated the evolution of genes critical in Agrobacterium fitness and ecology. For the type VI secretion system (T6SS) involved in interbacterial competition, multiple losses and one horizontal gene transfer (HGT) event were inferred. For the tumor-inducing plasmids (pTi) and the pTi-encoded type IV secretion system (T4SS) that determine Agrobacterium phytopathogenicity, the evolution of these accessory replicons was decoupled from the chromosomes, thus contributing to another level of complexity. Intriguingly, for both T6SS and T4SS, genes that encode the structural components are highly conserved, whereas extensive diversity exists at multiple levels (i.e., between-species, within-species, intra-genome, and intra-gene) for genes that encode effectors and associated proteins. These findings suggest that opposite modes of selection may act on components conferring different functions within a system. In conclusion, this work provides insights into the genomic diversification of these bacteria and sheds light on the modularity of their molecular evolution.

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“…The chromosomal regions encoding Rhs repeats were originally described in Escherichia coli genomes as sites where recombination frequently took place 17 . Later studies revealed that Rhs repeat-containing proteins are not unique to E. coli but are common across Proteobacteria 18, 19 . Other more distant homologs, called teneurins, are involved in axon guidance in vertebrates 20–22 .…”

Section: Introductionmentioning

confidence: 99%

Structure of a bacterial Rhs effector exported by the type VI secretion system

Guenther

Quentin

Ahmad

et al. 2021

Preprint

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The type VI secretion system (T6SS) is a widespread protein export apparatus found in Gram-negative bacteria. The majority of T6SSs deliver toxic effector proteins into competitor bacteria. Yet, the structure, function, and activation of many of these effectors remains poorly understood. Here, we present the structures of the T6SS effector RhsA from Pseudomonas protegens and its cognate T6SS spike protein, VgrG1, at 3.3 Å resolution. The structures reveal that the rearrangement hotspot (Rhs) repeats of RhsA assemble into a closed anticlockwise β-barrel spiral similar to that found in bacterial insecticidal Tc toxins and in metazoan teneurin proteins. We find that the C-terminal toxin domain of RhsA is autoproteolytically cleaved but remains inside the Rhs ′cocoon′ where, with the exception of three ordered structural elements, most of the toxin is disordered. The N-terminal ′plug′ domain is unique to T6SS Rhs proteins and resembles a champagne cork that seals the Rhs cocoon at one end while also mediating interactions with VgrG1. Interestingly, this domain is also autoproteolytically cleaved inside the cocoon but remains associated with it. We propose that mechanical force is required to remove the cleaved part of the plug, resulting in the release of the toxin domain as it is delivered into a susceptible bacterial cell by the T6SS.

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Activity, delivery, and diversity of Type VI secretion effectors

Cited by 103 publications

References 119 publications

Large-scale discovery of candidate type VI secretion effectors with antibacterial activity

Large-scale discovery of candidate type VI secretion effectors with antibacterial activity

Modular evolution of secretion systems and virulence plasmids in a bacterial species complex

Structure of a bacterial Rhs effector exported by the type VI secretion system

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