Rules of Engagement: The Type VI Secretion System in Vibrio cholerae

Joshi, Avatar; Kostiuk, Benjamin; Rogers, Alisdair; Teschler, Jennifer K.; Pukatzki, Stefan; Yildiz, Fitnat H.

doi:10.1016/j.tim.2016.12.003

Cited by 107 publications

(104 citation statements)

References 96 publications

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“…The cavity around VgrG/PAAR spike is~1,110 × 10 3 Å 3 large and may accommodate up to~450-kDa large proteins, or three copies of up to~150-kDa protein. This is consistent with sizes of known effectors: 129-kDa VgrG-1, 113-kDa VgrG-3, or 155-kDa pair VasX-VasW (Dong et al, 2013;Joshi et al, 2017). Since 77-kDa VgrG-2 with no extension domain is required for T6SS assembly (Appendix Fig S3; Pukatzki et al, 2007), there is also enough space for effectors interacting with VgrGs, such as 72-kDa TseL (Dong et al, 2013), in agreement with the model that many effectors bind to the VgrG/PAAR spike ( Fig EV6; Shneider et al, 2013).…”

Section: Discussionsupporting

confidence: 86%

Cryo‐ EM reconstruction of Type VI secretion system baseplate and sheath distal end

et al. 2017

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The bacterial Type VI secretion system (T6SS) assembles from three major parts: a membrane complex that spans inner and outer membranes, a baseplate, and a sheath–tube polymer. The baseplate assembles around a tip complex with associated effectors and connects to the membrane complex by TssK. The baseplate assembly initiates sheath–tube polymerization, which in some organisms requires TssA. Here, we analyzed both ends of isolated non‐contractile Vibrio cholerae sheaths by cryo‐electron microscopy. Our analysis suggests that the baseplate, solved to an average 8.0 Å resolution, is composed of six subunits of TssE/F2/G and the baseplate periphery is decorated by six TssK trimers. The VgrG/PAAR tip complex in the center of the baseplate is surrounded by a cavity, which may accommodate up to ~450 kDa of effector proteins. The distal end of the sheath, resolved to an average 7.5 Å resolution, shows sixfold symmetry; however, its protein composition is unclear. Our structures provide an important step toward an atomic model of the complete T6SS assembly.

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Section: Discussionsupporting

confidence: 86%

Cryo‐ EM reconstruction of Type VI secretion system baseplate and sheath distal end

et al. 2017

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“…T6SS effectors are toxic to eukaryotic and prokaryotic cells (Joshi et al, 2017). For example, interactions between the V. cholerae T6SS and eukaryotic cells have been implicated in intestinal inflammation, and recent studies have linked interactions between the T6SS and the endogenous microbiome to the virulence of V. cholerae (Fast et al, 2018a;Ma and Mekalanos, 2010;Zhao et al, 2018).…”

Section: Ipc Suppression Of Growth In Response To the T6ss Requires Imentioning

confidence: 99%

Complex symbiont-pathogen interactions inhibit intestinal repair

Fast

Petkau

Ferguson

et al. 2019

Preprint

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SUMMARYPathogen-mediated damage to the intestinal epithelium activates compensatory growth and differentiation repair programs in progenitor cells. Accelerated progenitor growth replenishes damaged tissue and maintains barrier integrity. Despite the importance of epithelial renewal to intestinal homeostasis, we know little about the effects of pathogen-commensal interactions on progenitor growth. We found that the enteric pathogen Vibrio cholerae, blocks critical growth and differentiation pathways in Drosophila progenitors despite extensive damage to the epithelial tissue. We showed that inhibition of epithelial repair requires interactions of the Vibrio cholerae type six secretion system with a complex community of symbiotic bacteria, and that elimination of the gut microbiome is sufficient to restore homeostatic growth in infected intestines. Together, this work highlights the importance of pathogen-symbiont interactions on intestinal immune responses and outlines a previously undescribed impact of the type six secretion system on pathogenesis.

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“…To explain the differences in T6SS activity and to provide insight into the T6SS's biological functions, it is, therefore, important to understand the underlying regulatory pathways in pandemic V. cholerae strains. Accordingly, several minor and major T6SS regulators have been identified in V. cholerae (Joshi et al ., ) by changing their abundance through deletion or forced expression of the respective genes, which resulted in changes in T6SS gene expression or T6SS activity. Two of these major regulators, TfoX and TfoY (Borgeaud et al ., ; Metzger et al ., ), contain TfoX‐like N‐ and C‐terminal domains and proteins containing such domains are usually annotated as regulators of natural competence for transformation due to the presence of these domains in the competence regulator Sxy of Haemophilus influenzae (Redfield, ) and TfoX in V. cholerae (Meibom et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Ecological implications of gene regulation by TfoX and TfoY among diverse Vibrio species

Metzger

Matthey

Stoudmann

et al. 2019

Environmental Microbiology

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Summary Bacteria of the genus Vibrio are common members of aquatic environments where they compete with other prokaryotes and defend themselves against grazing predators. A macromolecular protein complex called the type VI secretion system (T6SS) is used for both purposes. Previous research showed that the sole T6SS of the human pathogen V. cholerae is induced by extracellular (chitin) or intracellular (low c‐di‐GMP levels) cues and that these cues lead to distinctive signalling pathways for which the proteins TfoX and TfoY serve as master regulators. In this study, we tested whether the TfoX‐ and TfoY‐mediated regulation of T6SS, concomitantly with natural competence or motility, was conserved in non‐cholera Vibrio species, and if so, how these regulators affected the production of individual T6SSs in double‐armed vibrios. We show that, alongside representative competence genes, TfoX regulates at least one T6SS in all tested Vibrio species. TfoY, on the other hand, fostered motility in all vibrios but had a more versatile T6SS response in that it did not foster T6SS‐mediated killing in all tested vibrios. Collectively, our data provide evidence that the TfoX‐ and TfoY‐mediated signalling pathways are mostly conserved in diverse Vibrio species and important for signal‐specific T6SS induction.

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Rules of Engagement: The Type VI Secretion System in Vibrio cholerae

Cited by 107 publications

References 96 publications

Cryo‐ EM reconstruction of Type VI secretion system baseplate and sheath distal end

Cryo‐ EM reconstruction of Type VI secretion system baseplate and sheath distal end

Complex symbiont-pathogen interactions inhibit intestinal repair

Ecological implications of gene regulation by TfoX and TfoY among diverse Vibrio species

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