{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T18:09:20Z","timestamp":1789063760195,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014568","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000}}],"reference-count":121,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["NWA 1292.19.354"],"award-info":[{"award-number":["NWA 1292.19.354"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["09150172110006"],"award-info":[{"award-number":["09150172110006"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["101161713"],"award-info":[{"award-number":["101161713"]}],"id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology, Government of West Bengal","doi-asserted-by":"publisher","award":["BT\/INF\/22\/SP22844\/2017"],"award-info":[{"award-number":["BT\/INF\/22\/SP22844\/2017"]}],"id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["SR\/FST\/LSII-039\/2015"],"award-info":[{"award-number":["SR\/FST\/LSII-039\/2015"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology, Government of West Bengal","doi-asserted-by":"publisher","award":["BT\/PR54674\/BMS\/85\/475\/2024"],"award-info":[{"award-number":["BT\/PR54674\/BMS\/85\/475\/2024"]}],"id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    \u03b1-toxin (AT) is a potent pore-forming toxin that causes cell damage during infection. The structure and activity of AT have been studied extensively, but the environmental factors that modulate its toxicity remain unclear. Here, we demonstrate that the extracellular pH modulates AT cytotoxicity through two independent mechanisms in human cells. First, we show that acidic conditions enhance AT pore maturation, causing a toxin-intrinsic and ADAM10 independent increase in cytotoxicity after prolonged exposure to AT. Second, we demonstrate that both acidic and alkaline conditions impair the cellular capacity to internalize AT pores, resulting in toxin retention at the cell surface and increased cytotoxicity after pulse intoxication. The cell-intrinsic, pH-dependent sensitization to AT is observed in various human cell types but not for other pore forming toxins. Together, our findings indicate that the extracellular pH modulates AT activity and host cell susceptibility.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014568","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:50:18Z","timestamp":1788285018000},"page":"e1014568","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acidic and alkaline conditions enhance Staphylococcus aureus \u03b1-toxin pore formation and cytotoxicity"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0562-6357","authenticated-orcid":true,"given":"Tristan J.","family":"van der Linden","sequence":"first","affiliation":[{"name":"University Medical Center Utrecht","place":["Utrecht, The Netherlands"],"department":["Department of Medical Microbiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Indian Institute of Science","place":["Bengaluru, Karnataka, India"],"department":["Molecular Biophysics Unit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisette M.","family":"Scheepmaker","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht","place":["Utrecht, The Netherlands"],"department":["Department of Medical Microbiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debajyoti","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Indian Institute of Science","place":["Bengaluru, Karnataka, India"],"department":["Molecular Biophysics Unit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somnath","family":"Dutta","sequence":"additional","affiliation":[{"name":"Indian Institute of Science","place":["Bengaluru, Karnataka, India"],"department":["Molecular Biophysics Unit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart W.","family":"Bardoel","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht","place":["Utrecht, The Netherlands"],"department":["Department of Medical Microbiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5981-7259","authenticated-orcid":true,"given":"Andr\u00e1s N.","family":"Spaan","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht","place":["Utrecht, The Netherlands"],"department":["Department of Medical Microbiology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"issue":"8","key":"ppat.1014568.ref001","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"FD Lowy","year":"1998","journal-title":"N Engl J Med"},{"issue":"4","key":"ppat.1014568.ref002","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1097\/00005792-199407000-00002","article-title":"The current spectrum of Staphylococcus aureus infection in a tertiary care hospital","volume":"73","author":"DM Musher","year":"1994","journal-title":"Medicine (Baltimore)"},{"key":"ppat.1014568.ref003","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/9781444308464.ch29","article-title":"Clinical manifestations of community-acquired MRSA infections","author":"BS Schwartz","year":"2009","journal-title":"Staphylococci in human disease. John Wiley & Sons, Ltd"},{"issue":"11","key":"ppat.1014568.ref004","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nrmicro.2017.104","article-title":"The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota","volume":"15","author":"B Krismer","year":"2017","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1014568.ref005","doi-asserted-by":"crossref","first-page":"18033","DOI":"10.1038\/nrdp.2018.33","article-title":"Methicillin-resistant Staphylococcus aureus","volume":"4","author":"AS Lee","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"2","key":"ppat.1014568.ref006","article-title":"Immune evasion by Staphylococcus aureus","volume":"7","author":"NWM de Jong","year":"2019","journal-title":"Microbiol Spectr"},{"issue":"30","key":"ppat.1014568.ref007","doi-asserted-by":"crossref","first-page":"13473","DOI":"10.1073\/pnas.1001815107","article-title":"Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus 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