Type VI secretion system

Last updated

The type VI secretion system (T6SS) is molecular machine used by a wide range of Gram-negative bacterial species to transport effectors from the interior (cytoplasm or cytosol) of a bacterial cell across the cellular envelope into an adjacent target cell. While often reported that the T6SS was discovered in 2006 by researchers studying the causative agent of cholera, Vibrio cholerae , the first study demonstrating that T6SS genes encode a protein export apparatus was actually published in 2004, in a study of protein secretion by the fish pathogen Edwardsiella tarda . [1] [2] [3]

Contents

Since then, it is estimated that at least a quarter of all pathogenic and non-pathogenic proteobacterial genomes encode for a T6SS, including pathogens of animals, plants, and humans, as well as soil, environmental or marine bacteria. [4] [5] [6] [7] Genes encoding for the T6SSs are commonly found chromosomally, but can also be harboured in mobile genetic elements and on plasmids mediating their transfer and increase in genetic diversity. [8] [9] While most of the early studies of Type VI secretion focused on its role in the pathogenesis of higher organisms, it is now known to function primarily in interbacterial antagonism. [3]

Structure and mechanism

Type VI secretion system protein , Burkholderia pseudomallei. 3wx6.jpg
Type VI secretion system protein , Burkholderia pseudomallei.

The T6SS is thought to resemble an inverted phage extending outward from the bacterial cell surface. It consists of 14 proteins that assemble into three sub-complexes: a phage tail-like tubule, a phage baseplate-like structure, and cell-envelope spanning membrane complex. These three subcomplexes work together to transport proteins across the bacterial cell envelope and into a target cell through a contractile mechanism [10]

Structure of a Type VI Secretion System Untitled Diagram.jpg
Structure of a Type VI Secretion System

Phage tail-like

The phage tail-like component of the T6SS is a dynamic tubular structure that undergoes cycles of assembly and disassembly. It can be up to 600 nm long, and has been visualized extending across the bacterial cytoplasm in electron micrographs. [11] The tubules consist of repeating units of the proteins TssA and TssB (VipA/VipB) arranged as a sheath around a tube built from stacked hexameric rings of the haemolysin co-regulated protein (Hcp). [12] [13] At the tip of the Hcp tube sits a trimer of the phage tail spike-like protein VgrG, which is in turn capped by a pointed PAAR domain-containing protein. [14] Contraction of the sheath is thought to propel the Hcp tube, VgrG and associated substrates outside of the bacterial cell, where the VgrG/PAAR spike facilitates penetration of the membrane of a neighboring cell. The tubule structure is dismantled through the action of the ATP-degrading protein ClpV, which sits at the tubule base. [13]

Baseplate

The phage tail-like tubule of the T6SS assembles on a structure analogous to bacteriophage baseplates. It consists of the proteins TssE, TssF, TssG, and TssK. The baseplate and phage tail-like complex interact in the bacterial cytoplasm, and then are recruited to the cell envelope by the membrane complex. [10]

Membrane

The T6SS membrane complex is responsible for anchoring the apparatus to the cellular membrane, and provides the channel through which substrates are propelled by the contraction of the phage tail-like tubule. [10] This large (1.7 md) complex is formed from 10 interacting units of a heterotrimer containing TssJ, TssM and TssL. It is believed to span from the inner membrane to the outer membrane of the Gram negative bacterial cell envelope, forming a channel that opens and closes with a unique iris-like mechanism. [15]

Substrate recognition

Unlike substrates of other secretion systems (such as the general secretory pathway or secretion systems III and IV), those of the T6SS are not known to have any universally identifying features. Instead, they are recognized and selected for secretion through one of two structural components of the apparatus. One class of substrates binds within the pore of a hemolysin-coregulated protein (Hcp) hexamer. [16] Since substrates are unstable in the absence of this interaction, it is thought that the substrate-Hcp complexes are secreted together, rather than Hcp serving as a passive tubule through which substrates pass. Members of the second class of substrates are targeted for secretion via interaction with the phage tail spike-like protein VgrG. These substrates are often modular proteins, such as the Rhs toxins, that possess PAAR domain for interaction with VgrG at one end. [5] There are also instances where a VgrG and a substrate are both part of the same protein.[ citation needed ]

Anti-eukaryotic

Although the ancestral function of the T6SS appears to be targeting of bacteria, a handful of systems have been identified that have evolved to target eukaryotic cells. In general, these eukaryote-targeting systems are involved in causing disease. For example, the intracellular pathogen Francisella tularensis requires the activity of a T6SS to escape from phagosomes and replicate in the cytoplasm of macrophages. [17] The mechanism by which secreted proteins facilitate F. tularensis virulence is still unknown. The T6SS of Vibrio cholerae has a dual role, being able to target both bacterial and eukaryotic cells. [18] At least one substrate it secretes is specialized for eukaryotic cell-targeting, functioning by cross-linking the cytoskeleton protein actin. [19] Burkholderia pseudomallei and Edwardsiella tarda are two other organisms which possess a T6SS that appears dedicated for eukaryotic targeting. The T6SS of plant pathogen Xanthomonas citri protects it from predatory amoeba Dictyostelium discoideum . [20]

Antibacterial

The antibacterial mechanism in P. aeruginosa. P. aeruginosa have self-immunity to their own effector toxins: Tsi proteins bind and stabilise Tse toxins, preventing cell senescence and peptidoglycan cell wall lysis. Antibacterial Mechanisms of T6SS.jpg
The antibacterial mechanism in P. aeruginosa . P. aeruginosa have self-immunity to their own effector toxins: Tsi proteins bind and stabilise Tse toxins, preventing cell senescence and peptidoglycan cell wall lysis.

A wide range of Gram-negative bacteria have been shown to have antibacterial T6SSs, including opportunistic pathogens such as Pseudomonas aeruginosa, [21] obligate commensal species that inhabit the human gut ( Bacteroides spp.), [22] and plant-associated bacteria such as Agrobacterium tumefaciens . [23] These systems exert antibacterial activity via the function of their secreted substrates. [3] All characterized bacterial-targeting T6SS proteins act as toxins, either by killing or preventing the growth of target cells. The mechanisms of toxicity toward target cells exhibited by T6SS substrates are diverse, but typically involve targeting of highly conserved bacterial structures, including degradation of the cell wall through amidase or glycohydrolase activity, disruption of cell membranes through lipase activity or pore formation, cleavage of DNA, and degradation of the essential metabolite NAD+. [3] [24] T6SS-positive bacterial species prevent T6SS-mediated intoxication towards self and kin cells by producing immunity proteins specific to each secreted toxin. The immunity proteins function by binding to the toxin proteins, often at their active site, thereby blocking their activity. [25] [3]

Regulation

GacS/Rsm system

Some research has gone into regulation of T6SS by two component systems. In P. aeruginosa , it has been observed that the GacS/Rsm two-component system is involved in type VI secretion system regulation. This system regulates the expression of Rsm small regulatory RNA molecules, and has also been implicated in biofilm formation. Upon the GacS/Rsm pathway stimulation, an increase in Rsm molecules leads to inhibition of mRNA-binding protein RsmA. RsmA is a translational inhibitor that binds to sequences near the ribosome-binding site for T6SS gene expression. This level of regulation has also been observed in P. fluorescens and P. syringae . [26] [27]

Quorum sensing

There are various examples in which quorum sensing regulates T6SS. In Vibrio cholerae T6SS studies, it has been observed that serotype O37 has high vas gene expression. Serotypes O139 and O1 on the other hand exhibit the opposite, with markedly low vas gene expression. It has been suggested that the differences in expression are attributable to differences in quorum-sensing levels. In Vibrio cholerae , autoinducer-1 (AI-1) signals are detected by LuxQ, a sensor kinase. LuxQ activates LuxU, which then acts on LuxO, a DNA-binding protein which represses HapR gene expression. HapR is thought to LuxO deletions resulted in strong induction of vas gene expression, and hence T6SS expression, demonstrating that T6SS is regulated in some form by quorum sensing. [28] However, O1 strains with LuxO deletions still had relatively quiescent T6SS compared to the O37 strain, suggesting that additional factors are also involved. [29]

See also

Related Research Articles

<i>Vibrio cholerae</i> Species of bacterium

Vibrio cholerae is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimp, and other shellfish. Some strains of V. cholerae are pathogenic to humans and cause a deadly disease called cholera, which can be derived from the consumption of undercooked or raw marine life species.

<span class="mw-page-title-main">Chaperone (protein)</span> Proteins assisting in protein folding

In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis.

<span class="mw-page-title-main">Secretion</span> Controlled release of substances by cells or tissues

Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mechanism of cell secretion is via secretory portals at the plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structures embedded in the cell membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.

<span class="mw-page-title-main">Filamentous bacteriophage</span> Family of viruses

Filamentous bacteriophages are a family of viruses (Inoviridae) that infect bacteria, or bacteriophages. They are named for their filamentous shape, a worm-like chain, about 6 nm in diameter and about 1000-2000 nm long. This distinctive shape reflects their method of replication: the coat of the virion comprises five types of viral protein, which are located in the inner membrane of the host bacterium during phage assembly, and these proteins are added to the nascent virion's DNA as it is extruded through the membrane. The simplicity of filamentous phages makes them an appealing model organism for research in molecular biology, and they have also shown promise as tools in nanotechnology and immunology.

<i>Vibrio parahaemolyticus</i> Species of bacterium

Vibrio parahaemolyticus (V. parahaemolyticus) is a curved, rod-shaped, Gram-negative bacterial species found in the sea and in estuaries which, when ingested, may cause gastrointestinal illness in humans. V. parahaemolyticus is oxidase positive, facultatively aerobic, and does not form spores. Like other members of the genus Vibrio, this species is motile, with a single, polar flagellum.

Bacterial display is a protein engineering technique used for in vitro protein evolution. Libraries of polypeptides displayed on the surface of bacteria can be screened using flow cytometry or iterative selection procedures (biopanning). This protein engineering technique allows us to link the function of a protein with the gene that encodes it. Bacterial display can be used to find target proteins with desired properties and can be used to make affinity ligands which are cell-specific. This system can be used in many applications including the creation of novel vaccines, the identification of enzyme substrates and finding the affinity of a ligand for its target protein.

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon.

The CTXφ bacteriophage is a filamentous bacteriophage. It is a positive-strand DNA virus with single-stranded DNA (ssDNA).

Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host, usually using a type 3 secretion system (TTSS/T3SS), a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). Some bacteria inject only a few effectors into their host’s cells while others may inject dozens or even hundreds. Effector proteins may have many different activities, but usually help the pathogen to invade host tissue, suppress its immune system, or otherwise help the pathogen to survive. Effector proteins are usually critical for virulence. For instance, in the causative agent of plague, the loss of the T3SS is sufficient to render the bacteria completely avirulent, even when they are directly introduced into the bloodstream. Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a membrane vesicle trafficking secretory pathway, in order to modify their environment or attack/invade target cells, for example, at the host-pathogen interface.

The type 2 secretion system is a type of protein secretion machinery found in various species of Gram-negative bacteria, including many human pathogens such as Pseudomonas aeruginosa and Vibrio cholerae. The type II secretion system is one of six protein secretory systems commonly found in Gram-negative bacteria, along with the type I, type III, and type IV secretion systems, as well as the chaperone/usher pathway, the autotransporter pathway/type V secretion system, and the type VI secretion system. Like these other systems, the type II secretion system enables the transport of cytoplasmic proteins across the lipid bilayers that make up the cell membranes of Gram-negative bacteria. Secretion of proteins and effector molecules out of the cell plays a critical role in signaling other cells and in the invasion and parasitism of host cells.

Polymorphic toxins (PTs) are multi-domain proteins primarily involved in competition between bacteria but also involved in pathogenesis when injected in eukaryotic cells. They are found in all major bacterial clades.

Rhs toxins belong to the polymorphic toxin category of bacterial exotoxins. Rhs proteins are widespread and can be produced by both Gram-negative and Gram-positive bacteria. Rhs toxins are very large proteins of usually more than 1,500 aminoacids with variable C-terminal toxic domains. Their toxic activity can either target eukaryotes or other bacteria.

Contact-dependent growth inhibition (CDI) is a phenomenon where a bacterial cell may deliver a polymorphic toxin molecule into neighbouring bacterial cells upon direct cell-cell contact, causing growth arrest or cell death.

<span class="mw-page-title-main">Bacterial secretion system</span> Protein complexes present on the cell membranes of bacteria for secretion of substances

Bacterial secretion systems are protein complexes present on the cell membranes of bacteria for secretion of substances. Specifically, they are the cellular devices used by pathogenic bacteria to secrete their virulence factors to invade the host cells. They can be classified into different types based on their specific structure, composition and activity. Generally, proteins can be secreted through two different processes. One process is a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and delivered directly through the cell membrane into the host cell. Another involves a two-step activity in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally through the outer cell membrane into the host cell.

A protein-sorting transpeptidase is an enzyme, such as the sortase SrtA of Staphylococcus aureus, that cleaves one or more target proteins produced by the same cell, as part of a specialized pathway of protein targeting. The typical prokaryotic protein-sorting transpeptidase is characterized as a protease, but does not simply hydrolyze a peptide bond. Instead, the larger, N-terminal portion of the cleaved polypeptide is transferred onto another molecule, such as a precursor of the peptidoglycan cell wall in Gram-positive bacteria.

The bacterial type IV secretion system, also known as the type IV secretion system or the T4SS, is a secretion protein complex found in gram negative bacteria, gram positive bacteria, and archaea. It is able to transport proteins and DNA across the cell membrane. The type IV secretion system is just one of many bacterial secretion systems. Type IV secretion systems are related to conjugation machinery which generally involve a single-step secretion system and the use of a pilus. Type IV secretion systems are used for conjugation, DNA exchange with the extracellular space, and for delivering proteins to target cells. The type IV secretion system is divided into type IVA and type IVB based on genetic ancestry.

John Mekalanos is a microbiologist who is primarily known for leading one of the first teams that reported the discovery of the type VI secretion system as well as his work on the pathogenicity of the bacterial species Vibrio cholerae, its toxin, and its secretion systems. Since 1998, he has been a member of the National Academy of Sciences.

<span class="mw-page-title-main">Alain Filloux</span> French microbiologist

Alain Ange-Marie Filloux is a French/British microbiologist who is a Professor of Molecular Microbiology at Imperial College London. His research looks at the chronic infection of Pseudomonas aeruginosa, a Gram-negative bacterium that causes nosocomial infections in people who are immunocompromised and a deadly threat for cystic fibrosis patients.

References

  1. ↑ Rao PS, Yamada Y, Tan YP, Leung KY (2004). "Use of proteomics to identify novel virulence determinants that are required for Edwardsiella tarda pathogenesis". Mol Microbiol. 53 (2): 573–86. doi: 10.1111/j.1365-2958.2004.04123.x . PMID   15228535. S2CID   25901071.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ↑ Hood RD, Peterson SB, Mougous JD (March 2017). "From Striking Out to Striking Gold: Discovering that Type VI Secretion Targets Bacteria". Cell Host & Microbe. 21 (3): 286–289. doi:10.1016/j.chom.2017.02.001. PMC   6404758 . PMID   28279332.
  3. 1 2 3 4 5 Russell AB, Peterson SB, Mougous JD (February 2014). "Type VI secretion system effectors: poisons with a purpose". Nature Reviews. Microbiology. 12 (2): 137–48. doi:10.1038/nrmicro3185. PMC   4256078 . PMID   24384601.
  4. ↑ Boyer, Frédéric; Fichant, Gwennaële; Berthod, Jérémie; Vandenbrouck, Yves; Attree, Ina (December 2009). "Dissecting the bacterial type VI secretion system by a genome wide in silico analysis: what can be learned from available microbial genomic resources?". BMC Genomics. 10 (1): 104. doi: 10.1186/1471-2164-10-104 . ISSN   1471-2164. PMC   2660368 . PMID   19284603.
  5. 1 2 Shneider MM, Buth SA, Ho BT, Basler M, Mekalanos JJ, Leiman PG (August 2013). "PAAR-repeat proteins sharpen and diversify the type VI secretion system spike". Nature. 500 (7462): 350–353. Bibcode:2013Natur.500..350S. doi:10.1038/nature12453. PMC   3792578 . PMID   23925114.
  6. ↑ Bingle, Lewis EH; Bailey, Christopher M; Pallen, Mark J (February 2008). "Type VI secretion: a beginner's guide". Current Opinion in Microbiology. 11 (1): 3–8. doi:10.1016/j.mib.2008.01.006. PMID   18289922.
  7. ↑ Monjarás Feria, Julia; Valvano, Miguel A. (2020-10-19). "An Overview of Anti-Eukaryotic T6SS Effectors". Frontiers in Cellular and Infection Microbiology. 10: 584751. doi: 10.3389/fcimb.2020.584751 . ISSN   2235-2988. PMC   7641602 . PMID   33194822.
  8. ↑ Robinson, Luca; Liaw, Janie; Omole, Zahra; Xia, Dong; van Vliet, Arnoud H. M.; Corcionivoschi, Nicolae; Hachani, Abderrahman; Gundogdu, Ozan (29 June 2021). "Bioinformatic analysis of the Campylobacter jejuni Type VI secretion system and effector prediction". Frontiers in Microbiology. 12: 1751. doi: 10.3389/fmicb.2021.694824 . ISSN   1664-302X. PMC   8285248 . PMID   34276628.
  9. ↑ Filloux, Alain; Hachani, Abderrahman; Bleves, Sophia (June 2008). "The bacterial type VI secretion machine: yet another player for protein transport across membranes". Microbiology. 154 (6): 1570–1583. doi: 10.1099/mic.0.2008/016840-0 . hdl: 10044/1/40505 . PMID   18524912.
  10. 1 2 3 Cianfanelli FR, Monlezun L, Coulthurst SJ (January 2016). "Aim, Load, Fire: The Type VI Secretion System, a Bacterial Nanoweapon". Trends in Microbiology. 24 (1): 51–62. doi:10.1016/j.tim.2015.10.005. PMID   26549582.
  11. ↑ Basler M, Pilhofer M, Henderson GP, Jensen GJ, Mekalanos JJ (February 2012). "Type VI secretion requires a dynamic contractile phage tail-like structure". Nature. 483 (7388): 182–6. Bibcode:2012Natur.483..182B. doi:10.1038/nature10846. PMC   3527127 . PMID   22367545.
  12. ↑ Brunet YR, Hénin J, Celia H, Cascales E (March 2014). "Type VI secretion and bacteriophage tail tubes share a common assembly pathway". EMBO Reports. 15 (3): 315–21. doi:10.1002/embr.201337936. PMC   3989698 . PMID   24488256.
  13. 1 2 Bönemann G, Pietrosiuk A, Diemand A, Zentgraf H, Mogk A (February 2009). "Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion". The EMBO Journal. 28 (4): 315–25. doi:10.1038/emboj.2008.269. PMC   2646146 . PMID   19131969.
  14. ↑ Bönemann G, Pietrosiuk A, Diemand A, Zentgraf H, Mogk A (February 2009). "Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion". The EMBO Journal. 28 (4): 315–25. doi:10.1038/emboj.2008.269. PMC   2646146 . PMID   19131969.
  15. ↑ Durand E, Nguyen VS, Zoued A, Logger L, Péhau-Arnaudet G, Aschtgen MS, Spinelli S, Desmyter A, Bardiaux B, Dujeancourt A, Roussel A, Cambillau C, Cascales E, Fronzes R (July 2015). "Biogenesis and structure of a type VI secretion membrane core complex". Nature. 523 (7562): 555–60. Bibcode:2015Natur.523..555D. doi:10.1038/nature14667. PMID   26200339. S2CID   205244835.
  16. ↑ Silverman JM, Agnello DM, Zheng H, Andrews BT, Li M, Catalano CE, Gonen T, Mougous JD (September 2013). "Haemolysin coregulated protein is an exported receptor and chaperone of type VI secretion substrates". Molecular Cell. 51 (5): 584–93. doi:10.1016/j.molcel.2013.07.025. PMC   3844553 . PMID   23954347.
  17. ↑ Nano FE, Schmerk C (June 2007). "The Francisella pathogenicity island". Annals of the New York Academy of Sciences. 1105 (1): 122–37. Bibcode:2007NYASA1105..122N. doi:10.1196/annals.1409.000. PMID   17395722. S2CID   35958075.
  18. ↑ Dong TG, Ho BT, Yoder-Himes DR, Mekalanos JJ (February 2013). "Identification of T6SS-dependent effector and immunity proteins by Tn-seq in Vibrio cholerae". Proceedings of the National Academy of Sciences of the United States of America. 110 (7): 2623–8. Bibcode:2013PNAS..110.2623D. doi: 10.1073/pnas.1222783110 . PMC   3574944 . PMID   23362380.,
  19. ↑ Pukatzki S, Ma AT, Revel AT, Sturtevant D, Mekalanos JJ (September 2007). "Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin". Proceedings of the National Academy of Sciences of the United States of America. 104 (39): 15508–13. Bibcode:2007PNAS..10415508P. doi: 10.1073/pnas.0706532104 . PMC   2000545 . PMID   17873062.,
  20. ↑ Bayer-Santos E, Lima LD, Ceseti LM, Ratagami CY, de Santana ES, da Silva AM, Farah CS, Alvarez-Martinez CE (April 2018). "Xanthomonas citri T6SS mediates resistance to Dictyostelium predation and is regulated by an ECF σ factor and cognate Ser/Thr kinase". Environmental Microbiology. 20 (4): 1562–1575. doi:10.1111/1462-2920.14085. PMID   29488354. S2CID   3579518.
  21. ↑ Hood RD, Singh P, Hsu F, Güvener T, Carl MA, Trinidad RR, Silverman JM, Ohlson BB, Hicks KG, Plemel RL, Li M, Schwarz S, Wang WY, Merz AJ, Goodlett DR, Mougous JD (January 2010). "A type VI secretion system of Pseudomonas aeruginosa targets a toxin to bacteria". Cell Host & Microbe. 7 (1): 25–37. doi:10.1016/j.chom.2009.12.007. PMC   2831478 . PMID   20114026.
  22. ↑ Russell AB, Wexler AG, Harding BN, Whitney JC, Bohn AJ, Goo YA, Tran BQ, Barry NA, Zheng H, Peterson SB, Chou S, Gonen T, Goodlett DR, Goodman AL, Mougous JD (August 2014). "A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism". Cell Host & Microbe. 16 (2): 227–236. doi:10.1016/j.chom.2014.07.007. PMC   4136423 . PMID   25070807.
  23. ↑ Ma LS, Hachani A, Lin JS, Filloux A, Lai EM (July 2014). "Agrobacterium tumefaciens deploys a superfamily of type VI secretion DNase effectors as weapons for interbacterial competition in planta". Cell Host & Microbe. 16 (1): 94–104. doi:10.1016/j.chom.2014.06.002. PMC   4096383 . PMID   24981331.
  24. ↑ Whitney JC, Quentin D, Sawai S, LeRoux M, Harding BN, Ledvina HE, Tran BQ, Robinson H, Goo YA, Goodlett DR, Raunser S, Mougous JD (October 2015). "An interbacterial NAD(P)(+) glycohydrolase toxin requires elongation factor Tu for delivery to target cells". Cell. 163 (3): 607–19. doi:10.1016/j.cell.2015.09.027. PMC   4624332 . PMID   26456113.
  25. ↑ Ho BT, Dong TG, Mekalanos JJ (January 2014). "A view to a kill: the bacterial type VI secretion system". Cell Host & Microbe. 15 (1): 9–21. doi:10.1016/j.chom.2013.11.008. PMC   3936019 . PMID   24332978.
  26. ↑ Mougous JD, Cuff ME, Raunser S, Shen A, Zhou M, Gifford CA, Goodman AL, Joachimiak G, Ordoñez CL, Lory S, Walz T, Joachimiak A, Mekalanos JJ (June 2006). "A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus". Science. 312 (5779): 1526–30. Bibcode:2006Sci...312.1526M. doi:10.1126/science.1128393. PMC   2800167 . PMID   16763151.
  27. ↑ Records AR, Gross DC (July 2010). "Sensor kinases RetS and LadS regulate Pseudomonas syringae type VI secretion and virulence factors". Journal of Bacteriology. 192 (14): 3584–96. doi:10.1128/JB.00114-10. PMC   2897360 . PMID   20472799.
  28. ↑ Records AR, Gross DC (July 2010). "Sensor kinases RetS and LadS regulate Pseudomonas syringae type VI secretion and virulence factors". Journal of Bacteriology. 192 (14): 3584–96. doi:10.1128/JB.00114-10. PMC   2897360 . PMID   20472799.
  29. ↑ Silverman JM, Brunet YR, Cascales E, Mougous JD (2012). "Structure and regulation of the type VI secretion system". Annual Review of Microbiology. 66: 453–72. doi:10.1146/annurev-micro-121809-151619. PMC   3595004 . PMID   22746332.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.