Type 6 Secretion Dynamics Within and Between Bacterial Cells

Basler, Marek; Mekalanos, John J.

doi:10.1126/science.1222901

Cited by 213 publications

(293 citation statements)

References 11 publications

(20 reference statements)

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“…In that case, the membrane complex could induce changes in TssK structure, which would propagate through its interaction with TssE/F/G wedge to trigger sheath contraction. However, live‐cell imaging of T6SS sheath dynamics in V. cholerae provided no evidence for a triggering mechanism based on cell–cell contact (Basler & Mekalanos, 2012; Basler et al , 2012). Conversely, it is possible that rearrangement of baseplate proteins prior to sheath contraction changes TssK conformation, and this results in opening of the connected membrane complex to allow passage of the cargo‐loaded spike and tube.…”

Section: Discussionmentioning

confidence: 99%

“…Rapid sheath contraction propels the tip complex at the end of the inner tube formed from stacks of Hcp rings into the target cell periplasm or cytosol (Vettiger & Basler, 2016). In contrast to phages and many other contractile nanomachines, which translocate proteins only once by a single sheath contraction (Nakayama et al , 2000; Ge et al , 2015; Hu et al , 2015), the contracted T6SS sheath is disassembled by a cytosolic unfoldase ClpV or ClpB to allow for repeated protein secretion (Bönemann et al , 2009; Pietrosiuk et al , 2011; Basler & Mekalanos, 2012; Basler et al , 2012; Kapitein et al , 2013; Förster et al , 2014; Brodmann et al , 2017). …”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…Functional and structural studies have shown that the T6SS nanomachine shares striking similarities with the bacteriophage tail structure (14)(15)(16)(17)(18)(19)(20)(21)(22). Accumulating evidence suggests that the baseplate complex is recruited into the membrane-associated protein complex and initiates the polymerization of a TssB-TssC (VipAVipB) contractile sheath.…”

mentioning

confidence: 99%

VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor–effector complex

Bondage

Lin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

142

273

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Type VI secretion system (T6SS) is a macromolecular machine used by many Gram-negative bacteria to inject effectors/toxins into eukaryotic hosts or prokaryotic competitors for survival and fitness. To date, our knowledge of the molecular determinants and mechanisms underlying the transport of these effectors remains limited. Here, we report that two T6SS encoded valine-glycine repeat protein G (VgrG) paralogs in Agrobacterium tumefaciens C58 specifically control the secretion and interbacterial competition activity of the type VI DNase toxins Tde1 and Tde2. Deletion and domain-swapping analysis identified that the C-terminal extension of VgrG1 specifically confers Tde1 secretion and Tde1-dependent interbacterial competition activity in planta, and the C-terminal variable region of VgrG2 governs this specificity for Tde2. Functional studies of VgrG1 and VgrG2 variants with stepwise deletion of the C terminus revealed that the C-terminal 31 aa (C31) of VgrG1 and 8 aa (C8) of VgrG2 are the molecular determinants specifically required for delivery of each cognate Tde toxin. Further in-depth studies on Tde toxin delivery mechanisms revealed that VgrG1 interacts with the adaptor/chaperone-effector complex (Tap-1-Tde1) in the absence of proline-alanine-alanine-arginine (PAAR) and the VgrG1-PAAR complex forms independent of Tap-1 and Tde1. Importantly, we identified the regions involved in these interactions. Although the entire C31 segment is required for binding with the Tap-1-Tde1 complex, only the first 15 aa of this region are necessary for PAAR binding. These results suggest that the VgrG1 C terminus interacts sequentially or simultaneously with the Tap-1-Tde1 complex and PAAR to govern Tde1 translocation across bacterial membranes and delivery into target cells for antibacterial activity.type VI secretion system | VgrG | DNase effector | interbacterial competition | Agrobacterium tumefaciens

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“…The inner tube (composed of Hcp protein) is thought to carry toxic effector proteins within its lumen or on its tip, which is decorated with VgrG and PAAR proteins (4,6,7). Given that some cells can detect T6SS attack but not suffer any measurable loss in viability (8,9), it would seem that cell killing is likely due to the toxicity of effectors rather than membrane disruptions caused by insertion of the spear-like VgrG/PAAR/Hcp tube complex. T6SS-dependent effectors can attack a number of essential cellular targets, including the cell wall (10,11), membranes (11,12), and nucleic acids (13), and thus can mimic the actions of antibiotics and bacteriocins.…”

mentioning

confidence: 99%

Generation of reactive oxygen species by lethal attacks from competing microbes

Dong

Catalano

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

136

125

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Whether antibiotics induce the production of reactive oxygen species (ROS) that contribute to cell death is an important yet controversial topic. Here, we report that lethal attacks from bacterial and viral species also result in ROS production in target cells. Using soxS as an ROS reporter, we found soxS was highly induced in Escherichia coli exposed to various forms of attacks mediated by the type VI secretion system (T6SS), P1vir phage, and polymyxin B. Using a fluorescence ROS probe, we found enhanced ROS levels correlate with induced soxS in E. coli expressing a toxic T6SS antibacterial effector and in E. coli treated with P1vir phage or polymyxin B. We conclude that both contact-dependent and contact-independent interactions with aggressive competing bacterial species and viruses can induce production of ROS in E. coli target cells.T6SS | reactive oxygen species | interspecies competition | antibiotics |

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Type 6 Secretion Dynamics Within and Between Bacterial Cells

Cited by 213 publications

References 11 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

VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor–effector complex

Generation of reactive oxygen species by lethal attacks from competing microbes

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