Editing Staphylococcus aureus (section)

=== Type VII secretion system ===
{{See also|Type VII secretion system|l1=Type VII secretion system (T7SS)}}
A secretion system is a highly specialised multi-protein unit that is embedded in the cell envelope with the function of translocating effector proteins from inside of the cell to the extracellular space or into a target host cytosol. The exact structure and function of T7SS is yet to be fully elucidated. Currently, four proteins are known components of ''S. aureus'' type VII secretion system; EssC is a large integral membrane [[ATPase]] – which most likely powers the secretion systems and has been hypothesised forming part of the translocation channel. The other proteins are EsaA, EssB, EssA, that are membrane proteins that function alongside EssC to mediate protein secretion. The exact mechanism of how substrates reach the cell surface is unknown, as is the interaction of the three membrane proteins with each other and EssC.<ref name=":3">{{cite journal | vauthors = Bowman L, Palmer T | title = The Type VII Secretion System of ''Staphylococcus'' | journal = Annual Review of Microbiology | volume = 75 | issue = 1 | pages = 471–494 | date = October 2021 | pmid = 34343022 | doi = 10.1146/annurev-micro-012721-123600 | s2cid = 236915377 }}</ref>

'''T7 dependent effector proteins'''

EsaD is DNA [[endonuclease]] toxin secreted by ''S. aureus'', has been shown to inhibit growth of competitor ''S. aureus'' strain ''in vitro''.<ref name=":4">{{cite journal | vauthors = Cao Z, Casabona MG, Kneuper H, Chalmers JD, Palmer T | title = The type VII secretion system of ''Staphylococcus aureus'' secretes a nuclease toxin that targets competitor bacteria | journal = Nature Microbiology | volume = 2 | issue = 1 | pages = 16183 | date = October 2016 | pmid = 27723728 | pmc = 5325307 | doi = 10.1038/nmicrobiol.2016.183 }}</ref> EsaD is cosecreted with [[Chaperone (protein)|chaperone]] EsaE, which stabilises EsaD structure and brings EsaD to EssC for secretion.<ref name=":4" /><ref name=":3" /> Strains that produce EsaD also co-produce EsaG, a cytoplasmic anti-toxin that protects the producer strain from EsaD's toxicity.<ref name=":4" />

TspA is another toxin that mediates intraspecies competition. It is a bacteriostatic toxin that has a membrane depolarising activity facilitated by its [[C-terminal domain]]. Tsai is a transmembrane protein that confers immunity to the producer strain of TspA, as well as the attacked strains. There is genetic variability of the C-terminal domain of TspA therefore, it seems like the strains may produce different TspA variants to increase competitiveness.<ref name=":5">{{cite journal | vauthors = Ulhuq FR, Gomes MC, Duggan GM, Guo M, Mendonca C, Buchanan G, Chalmers JD, Cao Z, Kneuper H, Murdoch S, Thomson S, Strahl H, Trost M, Mostowy S, Palmer T | title = A membrane-depolarizing toxin substrate of the ''Staphylococcus aureus'' type VII secretion system mediates intraspecies competition | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 117 | issue = 34 | pages = 20836–47 | date = August 2020 | pmid = 32769205 | pmc = 7456083 | doi = 10.1073/pnas.2006110117 | bibcode = 2020PNAS..11720836U | doi-access = free }}</ref>

Toxins that play a role in intraspecies competition confers an advantage by promoting successful colonisation in polymicrobial communities such as the nasopharynx and lung by outcompeting lesser strains.<ref name=":5" />

There are also T7 effector proteins that play role a in pathogenesis, for example mutational studies of ''S. aureus'' have suggested that EsxB and EsxC contribute to persistent infection in a murine abscess model.<ref>{{cite journal | vauthors = Burts ML, Williams WA, DeBord K, Missiakas DM | title = EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis of ''Staphylococcus aureus'' infections | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 4 | pages = 1169–74 | date = January 2005 | pmid = 15657139 | pmc = 545836 | doi = 10.1073/pnas.0405620102 | bibcode = 2005PNAS..102.1169B | doi-access = free }}</ref>

EsxX has been implicated in [[neutrophil]] lysis, therefore suggested as contributing to the evasion of host immune system. Deletion of ''essX'' in ''S. aureus'' resulted in significantly reduced resistance to neutrophils and reduced virulence in murine skin and blood infection models.<ref>{{cite journal | vauthors = Dai Y, Wang Y, Liu Q, Gao Q, Lu H, Meng H, Qin J, Hu M, Li M | title = A Novel ESAT-6 Secretion System-Secreted Protein EsxX of Community-Associated ''Staphylococcus aureus'' Lineage ST398 Contributes to Immune Evasion and Virulence | journal = Frontiers in Microbiology | volume = 8 | pages = 819 | date = 2017-05-05 | pmid = 28529509 | pmc = 5418362 | doi = 10.3389/fmicb.2017.00819 | doi-access = free }}</ref>

Altogether, T7SS and known secreted effector proteins are a strategy of pathogenesis by improving fitness against competitor ''S. aureus'' species as well as increased virulence via evading the innate immune system and optimising persistent infections.{{citation needed|date=August 2022}}