Editing Helicobacter pylori (section)

===VacA===
'''VacA''' (vacuolating cytotoxin autotransporter) is another major virulence factor encoded by the ''vacA'' gene.<ref name="UniProt2">{{cite web |title=UniProt |url=https://www.uniprot.org/uniprotkb/Q48245/entry |website=www.uniprot.org |access-date=21 March 2024}}</ref> All strains of ''H. pylori'' carry this gene but there is much diversity, and only 50% produce the encoded cytotoxin.<ref name="Li"/><ref name="Alzahrani"/> The four main subtypes of ''vacA'' are ''s1/m1, s1/m2, s2/m1,'' and ''s2/m2''. ''s1/m1'' and ''s1/m2'' are known to cause an increased risk of gastric cancer.<ref>{{cite journal | vauthors = Miehlke S, Yu J, Schuppler M, Frings C, Kirsch C, Negraszus N, Morgner A, Stolte M, Ehninger G, Bayerdörffer E | title = Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease | journal = The American Journal of Gastroenterology | volume = 96 | issue = 4 | pages = 1008–13 | date = April 2001 | doi = 10.1111/j.1572-0241.2001.03685.x | pmid = 11316139 | s2cid = 24024542 | url = http://journals.lww.com/10.1111/j.1572-0241.2001.03685.x | access-date = 24 June 2020 | archive-date = 23 February 2022 | archive-url = https://web.archive.org/web/20220223203948/https://journals.lww.com/ajg/Abstract/2001/04000/Helicobacter_Pylori_Vaca,_Icea,andCagaStatus_and.17.aspx | url-status = live }}</ref> VacA is an oligomeric protein complex that causes a progressive vacuolation in the epithelial cells leading to their death.<ref name="Hisatsune"/> The vacuolation has also been associated with promoting intracellular reservoirs of ''H. pylori'' by disrupting the calcium channel cell membrane [[MCOLN1|TRPML1]].<ref>{{cite journal | vauthors = Capurro MI, Greenfield LK, Prashar A, Xia S, Abdullah M, Wong H, Zhong XZ, Bertaux-Skeirik N, Chakrabarti J, Siddiqui I, O'Brien C, Dong X, Robinson L, Peek RM, Philpott DJ, Zavros Y, Helmrath M, Jones NL | title = VacA generates a protective intracellular reservoir for Helicobacter pylori that is eliminated by activation of the lysosomal calcium channel TRPML1 | journal = Nature Microbiology | volume = 4 | issue = 8 | pages = 1411–1423 | date = August 2019 | pmid = 31110360 | pmc = 6938649 | doi = 10.1038/s41564-019-0441-6 }}</ref> VacA has been shown to increase the levels of [[Cyclooxygenase-2|COX2]], an up-regulation that increases the production of a [[prostaglandin]] indicating a strong host cell inflammatory response.<ref name="Hisatsune">{{cite journal |vauthors=Hisatsune J, Yamasaki E, Nakayama M, Shirasaka D, Kurazono H, Katagata Y, Inoue H, Han J, Sap J, Yahiro K, Moss J, Hirayama T |title=Helicobacter pylori VacA enhances prostaglandin E2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells |journal=Infect Immun |volume=75 |issue=9 |pages=4472–81 |date=September 2007 |pmid=17591797 |pmc=1951161 |doi=10.1128/IAI.00500-07 |url=}}</ref><ref>{{cite journal | vauthors = Sajib S, Zahra FT, Lionakis MS, German NA, Mikelis CM | title = Mechanisms of angiogenesis in microbe-regulated inflammatory and neoplastic conditions | journal = Angiogenesis | volume = 21 | issue = 1 | pages = 1–14 | date = February 2018 | pmid = 29110215 | doi = 10.1007/s10456-017-9583-4 | s2cid = 3346742 }}</ref>