{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:55:06Z","timestamp":1791320106766,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011686","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000}}],"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004805","name":"Ministry of Education of Perm Territory","doi-asserted-by":"publisher","award":["STARS\/APR2019\/BS\/730\/FS"],"award-info":[{"award-number":["STARS\/APR2019\/BS\/730\/FS"]}],"id":[{"id":"10.13039\/501100004805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>One of the mechanisms shaping the pathophysiology during the infection of enteric pathogen <jats:italic>Salmonella<\/jats:italic> Typhimurium is host PTM machinery utilization by the pathogen encoded effectors. <jats:italic>Salmonella<\/jats:italic> Typhimurium (<jats:italic>S<\/jats:italic>. Tm) during infection in host cells thrives in a vacuolated compartment, <jats:italic>Salmonella<\/jats:italic> containing vacuole (SCV), which sequentially acquires host endosomal and lysosomal markers. Long tubular structures, called as <jats:italic>Salmonella<\/jats:italic> induced filaments (SIFs), are further generated by <jats:italic>S<\/jats:italic>. Tm, which are known to be required for SCV\u2019s nutrient acquisition, membrane maintenance and stability. A tightly coordinated interaction involving prominent effector SifA and various host adapters PLEKHM1, PLEKHM2 and Rab GTPases govern SCV integrity and SIF formation. Here, we report for the first time that the functional regulation of SifA is modulated by PTM SUMOylation at its 11<jats:sup>th<\/jats:sup> lysine. <jats:italic>S<\/jats:italic>. Tm expressing SUMOylation deficient lysine 11 mutants of SifA (SifA<jats:sup>K11R<\/jats:sup>) is defective in intracellular proliferation due to compromised SIF formation and enhanced lysosomal acidification. Furthermore, murine competitive index experiments reveal defective <jats:italic>in vivo<\/jats:italic> proliferation and weakened virulence of SifA<jats:sup>K11R<\/jats:sup> mutant. Concisely, our data reveal that SifA<jats:sup>K11R<\/jats:sup> mutant nearly behaves like a SifA knockout strain which impacts Rab9-MPR mediated lysosomal acidification pathway, the outcome of which culminates in reduced bacterial load in <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> infection model systems. Our results bring forth a novel pathogen-host crosstalk mechanism where the SUMOylation of effector SifA regulated <jats:italic>S<\/jats:italic>. Tm intracellular survival.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011686","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T17:29:51Z","timestamp":1696008591000},"page":"e1011686","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["SifA SUMOylation governs Salmonella Typhimurium intracellular survival via modulation of lysosomal function"],"prefix":"10.1371","volume":"19","author":[{"given":"Hridya","family":"Chandrasekhar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayatree","family":"Mohapatra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirti","family":"Kajal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukesh","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kshitiz","family":"Walia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarika","family":"Rana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navneet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetal","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Tuli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasenjit","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9381-1213","authenticated-orcid":true,"given":"Chittur V.","family":"Srikanth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"ppat.1011686.ref001","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1086\/650733","article-title":"The global burden of nontyphoidal Salmonella gastroenteritis","volume":"50","author":"SE Majowicz","year":"2010","journal-title":"Clin Infect Dis"},{"key":"ppat.1011686.ref002","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/S1473-3099(19)30418-9","article-title":"The global burden of non-typhoidal salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017.","volume":"19","author":"JD Stanaway","year":"2019","journal-title":"The Lancet Infectious Diseases"},{"key":"ppat.1011686.ref003","doi-asserted-by":"crossref","first-page":"e0008732","DOI":"10.1371\/journal.pntd.0008732","article-title":"Non-typhoidal Salmonella infections among children in a tertiary hospital in Ningbo, Zhejiang, China, 2012\u20132019.","volume":"14","author":"Y Ke","journal-title":"PLOS Neglected Tropical Diseases [Internet]."},{"key":"ppat.1011686.ref004","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S1286-4579(00)00273-2","article-title":"Salmonella pathogenicity islands: big virulence in small packages","volume":"2","author":"SL Marcus","year":"2000","journal-title":"Microbes Infect"},{"key":"ppat.1011686.ref005","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S1097-2765(04)00053-X","article-title":"Control of actin turnover by a salmonella invasion protein","volume":"13","author":"EJ McGhie","year":"2004","journal-title":"Mol Cell"},{"key":"ppat.1011686.ref006","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3389\/fcimb.2019.00270","article-title":"Salmonella Pathogenicity Island 1 (SPI-1) and Its Complex Regulatory Network.","volume":"9","author":"L Lou","year":"2019","journal-title":"Front Cell Infect Microbiol [Internet]."},{"key":"ppat.1011686.ref007","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mib.2008.01.002","article-title":"The Salmonella-containing Vacuole\u2013Moving with the Times","volume":"11","author":"O. 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