Type VII secretion system

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Type VII secretion systems are bacterial secretion systems first observed in the phyla Actinomycetota and Bacillota . Bacteria use such systems to transport, or secrete, proteins into the environment. [1] The bacterial genus Mycobacterium uses type VII secretion systems (T7SS) to secrete proteins across their cell envelope. [2] The first T7SS system discovered was the ESX-1 System. [2]

Contents

T7SS has been studied as a virulence factor associated with the ESX-1 system in Mycobacterium tuberculosis . [2] These secretion systems are often found in gram-positive bacteria. Type VII secretion systems are necessary in Mycobacterium because of their impermeable membrane. [3] The RD1 locus or Gene for Type VII secretion can create a lytic effect through ESX-1 transport. [4]

Structure

Cryogenic electron microscopy was used to determine that a complex of two identical subunits made from four proteins forms the structure of the type VII secretion system in Mycobacterium smegmatis . [5] T7SS forms a six-sided complex that allows for nearly 165 membrane attachments. [6] This shows how complex the secretion system is. The MDa complex of the Type VII secretion system is found embedded in the inner membrane. [7]

The T7SS structure in Mycobacteria is 28.5 nm in width and 20 nm in height. This secretion system is composed of the following components: inner EccB5, outer EccB5, EccC5, inner EccD5, outer EccD5, EccE5 and MycP5. [7] These components make the 2.32-MDa complex. This complex is connected to an inner membrane by 165 transmembrane helices. [7] The membrane is composed of a trimer of dimers. The dimers are made up of one copy of MycP5, EccB5, EccC5, EccE5, and two copies of EccD5. [7] The MycP5 structure is what stabilizes the complex. Without the MycP5 complex, EccB5 copies cannot make the stable triangular scaffold. [7] In the membrane EccD5 create barrels that are hypothetically filled with lipids. [7] EccC is the only component of the T7SS that is present in all species that contain a type VII secretion system.

Mechanism

The core machinery of the Type VII secretion system is found in the inner membrane. Once this core machinery is assembled the Type VII secretion system exports alpha helical protein residues using ATP-ase. Type VII secretion systems use proteins from the ESX-1 system of secretion proteins. [8] T7SS uses unique proteins as compared to other secretion systems. [8]

Species distribution

Secretion systems are commonly found in gram-positive bacteria and Mycobacterium. There is also a system referred to as a T7SS in gram negative bacteria. [4]

In gram negative bacteria a Type VII ‘like" secretion system has been observed. It is known as the chaperone-usher fimbriae. This system helps gram negative bacteria colonize, form biofilms, and causes an increase in pathogenicity in the bacteria that utilize it. These systems are observable when genes for an Fimbrial usher protein (which is integral to the formation of a pilus in gram negative bacteria), a Chaperone (protein), and the building blocks of fimbriae are found together. [9]

The Type VII secretion system, however, was first observed in firmicutes and actinobacteria, specifically Mycobacterium tuberculosis. [10] [11] The type VII secretion system plays an important role in interbacterial competition, nutrient acquisition, and virulence in Firmicutes (which are spore-forming bacteria). [10] This type of secretion system has also been observed to play a role in the virulence and cytotoxicity of Streptococcus species. [12]

This system uses different proteins in order to function in varying species. The system alters itself and produces variants within each new species. These system variants are identified based on EssC- C terminus and other associated effectors. Variants have been observed in the following species: 4 variants in Group B streptococcus and staphylococcus aureus, and 7 variants within Listeria monocytogenes. [10] This type of secretion system also provides essential cell functions pathways with which to proceed. Mycobacteria have a cell membranes that are impenetrable, T7SS allow for substrates to pass through, making the Type VII Secretion system (also known as ESX) essential for mycobacterial growth and virulence. [3]

Role in virulence

T7SS plays a role in the virulence of mycobacterium. Disruption in the genes that encode T7SS called the RD1 locus results in the loss of function of secretion apparatus. [13] The genes necessary for ESX-1 transport have also been found outside of the RD1 locus. [14] This means that multiple genes are required for protein transport and disruption of these genes results in the loss of function in the secretion systems. [14] The ESX-1 system secretes polypeptides which causes a lytic effect though the specific polypeptide is not known. The extended RD1 (extRD1) region expresses membrane lytic activity in mycobacteria. The extRD1 genes are necessary for haemolysis activity. [15] Genetic changes to the ESX-1 system result in the loss of a secretion activity. In infection models this leads to a loss of virulence. [14]

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Mycobacterium is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy in humans. The Greek prefix myco- means 'fungus', alluding to this genus' mold-like colony surfaces. Since this genus has cell walls with a waxy lipid-rich outer layer that contains high concentrations of mycolic acid, acid-fast staining is used to emphasize their resistance to acids, compared to other cell types.

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

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<i>Mycobacterium smegmatis</i> Species of bacterium

Mycobacterium smegmatis is an acid-fast bacterial species in the phylum Actinomycetota and the genus Mycobacterium. It is 3.0 to 5.0 µm long with a bacillus shape and can be stained by Ziehl–Neelsen method and the auramine-rhodamine fluorescent method. It was first reported in November 1884 by Lustgarten, who found a bacillus with the staining appearance of tubercle bacilli in syphilitic chancres. Subsequent to this, Alvarez and Tavel found organisms similar to that described by Lustgarten also in normal genital secretions (smegma). This organism was later named M. smegmatis.

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<span class="mw-page-title-main">Outer membrane vesicle</span> Vesicles released from the outer membranes of Gram-negative bacteria

Outer membrane vesicles (OMVs) are vesicles released from the outer membranes of Gram-negative bacteria. While Gram-positive bacteria release vesicles as well those vesicles fall under the broader category of bacterial membrane vesicles (MVs). OMVs were the first MVs to be discovered, and are distinguished from outer inner membrane vesicles (OIMVS), which are gram-negative baterial vesicles containing portions of both the outer and inner bacterial membrane. Outer membrane vesicles were first discovered and characterized using transmission-electron microscopy by Indian Scientist Prof. Smriti Narayan Chatterjee and J. Das in 1966-67. OMVs are ascribed the functionality to provide a manner to communicate among themselves, with other microorganisms in their environment and with the host. These vesicles are involved in trafficking bacterial cell signaling biochemicals, which may include DNA, RNA, proteins, endotoxins and allied virulence molecules. This communication happens in microbial cultures in oceans, inside animals, plants and even inside the human body.

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References

  1. ↑ Spencer BL, Doran KS (July 2022). "Evolving understanding of the type VII secretion system in Gram-positive bacteria". PLOS Pathogens. 18 (7): e1010680. doi: 10.1371/journal.ppat.1010680 . PMC   9333272 . PMID   35901012.
  2. 1 2 3 Houben EN, Korotkov KV, Bitter W (August 2014). "Take five - Type VII secretion systems of Mycobacteria". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. Protein trafficking and secretion in bacteria. 1843 (8): 1707–1716. doi: 10.1016/j.bbamcr.2013.11.003 . PMID   24263244.
  3. 1 2 Beckham KS, Ciccarelli L, Bunduc CM, Mertens HD, Ummels R, Lugmayr W, et al. (April 2017). "Structure of the mycobacterial ESX-5 type VII secretion system membrane complex by single-particle analysis". Nature Microbiology. 2 (6): 17047. doi:10.1038/nmicrobiol.2017.47. hdl: 1871.1/350ffd47-20da-4c24-8b09-ce4ce2872e69 . PMID   28394313. S2CID   10602253.
  4. 1 2 Famelis N, Rivera-Calzada A, Degliesposti G, Wingender M, Mietrach N, Skehel JM, et al. (December 2019). "Architecture of the mycobacterial type VII secretion system". Nature. 576 (7786): 321–325. Bibcode:2019Natur.576..321F. doi:10.1038/s41586-019-1633-1. PMC   6914368 . PMID   31597161.
  5. ↑ Famelis N, Rivera-Calzada A, Degliesposti G, Wingender M, Mietrach N, Skehel JM, et al. (December 2019). "Architecture of the mycobacterial type VII secretion system". Nature. 576 (7786): 321–325. Bibcode:2019Natur.576..321F. doi:10.1038/s41586-019-1633-1. PMC   6914368 . PMID   31597161.
  6. ↑ "Structure of Type VII Secretion System Revealed". www.cssb-hamburg.de. Retrieved 2022-10-22.
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  8. 1 2 Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CM, et al. (November 2007). "Type VII secretion--mycobacteria show the way". Nature Reviews. Microbiology. 5 (11): 883–891. doi:10.1038/nrmicro1773. PMID   17922044. S2CID   11307957.
  9. ↑ Busch A, Waksman G (April 2012). "Chaperone-usher pathways: diversity and pilus assembly mechanism". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 367 (1592): 1112–1122. doi:10.1098/rstb.2011.0206. PMC   3297437 . PMID   22411982.
  10. 1 2 3 Spencer BL, Doran KS (July 2022). "Evolving understanding of the type VII secretion system in Gram-positive bacteria". PLOS Pathogens. 18 (7): e1010680. doi: 10.1371/journal.ppat.1010680 . PMC   9333272 . PMID   35901012.
  11. ↑ Tran HR, Grebenc DW, Klein TA, Whitney JC (March 2021). "Bacterial type VII secretion: An important player in host-microbe and microbe-microbe interactions". Molecular Microbiology. 115 (3): 478–489. doi: 10.1111/mmi.14680 . PMID   33410158. S2CID   230817692.
  12. ↑ Spencer BL, Tak U, Mendonça JC, Nagao PE, Niederweis M, Doran KS (December 2021). "A type VII secretion system in Group B Streptococcus mediates cytotoxicity and virulence". PLOS Pathogens. 17 (12): e1010121. doi: 10.1371/journal.ppat.1010121 . PMC   8675928 . PMID   34871327.
  13. ↑ Lewis KN, Liao R, Guinn KM, Hickey MJ, Smith S, Behr MA, Sherman DR (January 2003). "Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guérin attenuation". The Journal of Infectious Diseases. 187 (1): 117–23. doi:10.1086/345862. PMC   1458498 . PMID   12508154.
  14. 1 2 3 Kennedy GM, Hooley GC, Champion MM, Mba Medie F, Champion PA (May 2014). "A novel ESX-1 locus reveals that surface-associated ESX-1 substrates mediate virulence in Mycobacterium marinum". Journal of Bacteriology. 196 (10): 1877–1888. doi:10.1128/JB.01502-14. PMC   4011007 . PMID   24610712.
  15. ↑ Tran HR, Grebenc DW, Klein TA, Whitney JC (March 2021). "Bacterial type VII secretion: An important player in host-microbe and microbe-microbe interactions". Molecular Microbiology. 115 (3): 478–489. doi: 10.1111/mmi.14680 . PMID   33410158. S2CID   230817692.
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