A View to a Kill: the Bacterial Type VI Secretion System

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2013 Dec 17

PMID 24332978

Citations 321

Authors

Brian T Ho

Tao G Dong

John J Mekalanos

Affiliations

Soon will be listed here.

Abstract

The bacterial type VI secretion system (T6SS) is an organelle that is structurally and mechanistically analogous to an intracellular membrane-attached contractile phage tail. Recent studies determined that a rapid conformational change in the structure of a sheath protein complex propels T6SS spike and tube components along with antibacterial and antieukaryotic effectors out of predatory T6SS(+) cells and into prey cells. The contracted organelle is then recycled in an ATP-dependent process. T6SS is regulated at transcriptional and posttranslational levels, the latter involving detection of membrane perturbation in some species. In addition to directly targeting eukaryotic cells, the T6SS can also target other bacteria coinfecting a mammalian host, highlighting the importance of the T6SS not only for bacterial survival in environmental ecosystems, but also in the context of infection and disease. This review highlights these and other advances in our understanding of the structure, mechanical function, assembly, and regulation of the T6SS.

Citing Articles

Amidase and lysozyme dual functions in TseP reveal a new family of chimeric effectors in the type VI secretion system.

Wang Z, An Y, Zhao T, Pei T, Wang D, Liang X Elife. 2025; 13.

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The Type VI Secretion System of Sinorhizobium fredii USDA257 Is Required for Successful Nodulation With Glycine max cv Pekin.

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A VgrG2b fragment cleaved by caspase-11/4 promotes infection through suppressing the NLRP3 inflammasome.

Qian Y, Liu Q, Cheng X, Wang C, Kong C, Li M Elife. 2025; 13.

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Klebsiella pneumoniae employs a type VI secretion system to overcome microbiota-mediated colonization resistance.

Bray A, Broberg C, Hudson A, Wu W, Nagpal R, Islam M Nat Commun. 2025; 16(1):940.

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Distribution of the four type VI secretion systems in Pseudomonas aeruginosa and classification of their core and accessory effectors.

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References

Silverman J, Agnello D, Zheng H, Andrews B, Li M, Catalano C . Haemolysin coregulated protein is an exported receptor and chaperone of type VI secretion substrates. Mol Cell. 2013; 51(5):584-93. PMC: 3844553. DOI: 10.1016/j.molcel.2013.07.025. View

Zheng J, Shin O, Cameron D, Mekalanos J . Quorum sensing and a global regulator TsrA control expression of type VI secretion and virulence in Vibrio cholerae. Proc Natl Acad Sci U S A. 2010; 107(49):21128-33. PMC: 3000250. DOI: 10.1073/pnas.1014998107. View

Bonemann G, Pietrosiuk A, Diemand A, Zentgraf H, Mogk A . Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion. EMBO J. 2009; 28(4):315-25. PMC: 2646146. DOI: 10.1038/emboj.2008.269. View

Pell L, Kanelis V, Donaldson L, Howell P, Davidson A . The phage lambda major tail protein structure reveals a common evolution for long-tailed phages and the type VI bacterial secretion system. Proc Natl Acad Sci U S A. 2009; 106(11):4160-5. PMC: 2657425. DOI: 10.1073/pnas.0900044106. View

Gueguen E, Durand E, Zhang X, dAmalric Q, Journet L, Cascales E . Expression of a Yersinia pseudotuberculosis Type VI Secretion System Is Responsive to Envelope Stresses through the OmpR Transcriptional Activator. PLoS One. 2013; 8(6):e66615. PMC: 3686713. DOI: 10.1371/journal.pone.0066615. View

Michel-Briand Y, Baysse C . The pyocins of Pseudomonas aeruginosa. Biochimie. 2002; 84(5-6):499-510. DOI: 10.1016/s0300-9084(02)01422-0. View

Dong T, Mekalanos J . Characterization of the RpoN regulon reveals differential regulation of T6SS and new flagellar operons in Vibrio cholerae O37 strain V52. Nucleic Acids Res. 2012; 40(16):7766-75. PMC: 3439928. DOI: 10.1093/nar/gks567. View

English G, Trunk K, Rao V, Srikannathasan V, Hunter W, Coulthurst S . New secreted toxins and immunity proteins encoded within the Type VI secretion system gene cluster of Serratia marcescens. Mol Microbiol. 2012; 86(4):921-36. PMC: 3533786. DOI: 10.1111/mmi.12028. View

Kostyuchenko V, Leiman P, Chipman P, Kanamaru S, van Raaij M, Arisaka F . Three-dimensional structure of bacteriophage T4 baseplate. Nat Struct Biol. 2003; 10(9):688-93. DOI: 10.1038/nsb970. View

10.

Mougous J, Gifford C, Ramsdell T, Mekalanos J . Threonine phosphorylation post-translationally regulates protein secretion in Pseudomonas aeruginosa. Nat Cell Biol. 2007; 9(7):797-803. DOI: 10.1038/ncb1605. View

11.

Mougous J, Cuff M, Raunser S, Shen A, Zhou M, Gifford C . A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science. 2006; 312(5779):1526-30. PMC: 2800167. DOI: 10.1126/science.1128393. View

12.

Salomon D, Gonzalez H, Updegraff B, Orth K . Vibrio parahaemolyticus type VI secretion system 1 is activated in marine conditions to target bacteria, and is differentially regulated from system 2. PLoS One. 2013; 8(4):e61086. PMC: 3628861. DOI: 10.1371/journal.pone.0061086. View

13.

Dong T, Ho B, Yoder-Himes D, Mekalanos J . Identification of T6SS-dependent effector and immunity proteins by Tn-seq in Vibrio cholerae. Proc Natl Acad Sci U S A. 2013; 110(7):2623-8. PMC: 3574944. DOI: 10.1073/pnas.1222783110. View

14.

Koskiniemi S, Lamoureux J, Nikolakakis K, tKint de Roodenbeke C, Kaplan M, Low D . Rhs proteins from diverse bacteria mediate intercellular competition. Proc Natl Acad Sci U S A. 2013; 110(17):7032-7. PMC: 3637788. DOI: 10.1073/pnas.1300627110. View

15.

Felisberto-Rodrigues C, Durand E, Aschtgen M, Blangy S, Ortiz-Lombardia M, Douzi B . Towards a structural comprehension of bacterial type VI secretion systems: characterization of the TssJ-TssM complex of an Escherichia coli pathovar. PLoS Pathog. 2011; 7(11):e1002386. PMC: 3213119. DOI: 10.1371/journal.ppat.1002386. View

16.

Satchell K . Structure and function of MARTX toxins and other large repetitive RTX proteins. Annu Rev Microbiol. 2011; 65:71-90. DOI: 10.1146/annurev-micro-090110-102943. View

17.

Basler M, Mekalanos J . Type 6 secretion dynamics within and between bacterial cells. Science. 2012; 337(6096):815. PMC: 3557511. DOI: 10.1126/science.1222901. View

18.

Kitaoka M, Miyata S, Brooks T, Unterweger D, Pukatzki S . VasH is a transcriptional regulator of the type VI secretion system functional in endemic and pandemic Vibrio cholerae. J Bacteriol. 2011; 193(23):6471-82. PMC: 3232897. DOI: 10.1128/JB.05414-11. View

19.

Aschtgen M, Thomas M, Cascales E . Anchoring the type VI secretion system to the peptidoglycan: TssL, TagL, TagP... what else?. Virulence. 2010; 1(6):535-40. DOI: 10.4161/viru.1.6.13732. View

20.

Rodriguez-Rubio L, Gutierrez D, Martinez B, Rodriguez A, Gotz F, Garcia P . The tape measure protein of the Staphylococcus aureus bacteriophage vB_SauS-phiIPLA35 has an active muramidase domain. Appl Environ Microbiol. 2012; 78(17):6369-71. PMC: 3416594. DOI: 10.1128/AEM.01236-12. View