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Alliance"],"accepted":{"date-parts":[[2026,6,24]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Despite antibiotic therapy, 25\u201335% of patients with necrotizing soft tissue infections (NSTIs) die. The etiologic agents for NSTIs include\n                    <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                    and\n                    <jats:italic>Clostridium perfringens<\/jats:italic>\n                    , which secrete the cholesterol-dependent cytolysins (CDCs) streptolysin O and perfringolysin O to disrupt cell membranes. Whereas cells resist this damage by activating Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent repair pathways, including mitogen-activated protein kinase kinase (MEK)\u2013dependent microvesicle shedding, dysferlin-mediated patch repair, and annexin-mediated membrane clogging, the upstream regulators of these responses have remained elusive. Here, we demonstrated that the Rac guanine nucleotide exchange factor Vav2 accounts for almost all of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent repair against CDCs. Inhibiting or knocking down Vav2 sensitized multiple cell types to CDCs, whereas blocking other Rac guanine nucleotide exchange factors did not. Mechanistically, Vav2 triggered the critical mixed lineage kinase 3-MEK\u2013dependent repair pathway. MEK activation rescued repair in Vav2-inhibited cells. Blocking dysferlin or annexins failed to increase damage beyond Vav2 inhibition, suggesting Vav2 coordinates multiple repair pathways. Thus, Vav2 controls multiple Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated repair pathways that protect cells from CDCs produced during NSTIs.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202603633","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:00:21Z","timestamp":1783616421000},"page":"e202603633","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Vav2 is a master regulator of repair against bacterial pore-forming toxins"],"prefix":"10.26508","volume":"9","author":[{"given":"Victor Gbenga","family":"Kayejo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0405mnx93","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Sciences, Texas Tech University","place":[", Lubbock, TX, 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