{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:03:15Z","timestamp":1790622195240,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014640","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Salmonella<\/jats:italic>\n                    4,[5],12:i:- has emerged as a leading cause of non-typhoidal salmonellosis globally, yet the mechanisms governing its intracellular survival and pathogenic adaptation remain unclear. Herein, through transposon-insertion sequencing, we identify\n                    <jats:italic>nlpD<\/jats:italic>\n                    , a peptidoglycan hydrolase activator essential for maintaining membrane stability and facilitating bacterial division, as a critical gene for\n                    <jats:italic>Salmonella<\/jats:italic>\n                    infection.\n                    <jats:italic>nlpD<\/jats:italic>\n                    -deficient\n                    <jats:italic>Salmonella<\/jats:italic>\n                    exhibits significantly diminished survival in both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    settings. Mechanistically,\n                    <jats:italic>nlpD<\/jats:italic>\n                    deletion disrupts peptidoglycan and lipopolysaccharide homeostasis, rendering\n                    <jats:italic>Salmonella<\/jats:italic>\n                    more vulnerable to oxidative and acidic stresses within phagosomes. Accumulated cell wall components robustly activate the toll-like receptor-mediated NF-\u03baB signaling pathway, driving M1 macrophage polarization and autophagy-lysosomal activation to eliminate intracellular bacteria. An FDA-approved drug screen identifies ketoconazole as an NlpD-targeting compound that reduces bacterial loads in murine models. Our findings establish NlpD as a critical regulator that limits M1-polarized inflammatory responses, highlighting its potential as a therapeutic vulnerability against\n                    <jats:italic>Salmonella<\/jats:italic>\n                    4,[5],12:i:- infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014640","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:40:47Z","timestamp":1790098847000},"page":"e1014640","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transposon-insertion sequencing reveals NlpD as a vulnerability in intracellular survival and pathogenesis of Salmonella 4,[5],12:i:-"],"prefix":"10.1371","volume":"22","author":[{"given":"Mengping","family":"He","sequence":"first","affiliation":[{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinju","family":"Cai","sequence":"additional","affiliation":[{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Wu","sequence":"additional","affiliation":[{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqi","family":"Xu","sequence":"additional","affiliation":[{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine"]},{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Key Laboratory of Zoonosis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine"]},{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Key Laboratory of Zoonosis"]},{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Interdisciplinary Center for Zoonoses and Biosafety"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9622-6471","authenticated-orcid":true,"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine"]},{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Key Laboratory of Zoonosis"]},{"name":"Yangzhou University","place":["Yangzhou, China"],"department":["Jiangsu Interdisciplinary Center for Zoonoses and Biosafety"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"4","key":"ppat.1014640.ref001","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1128\/CMR.00002-15","article-title":"Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections","volume":"28","author":"JA Crump","year":"2015","journal-title":"Clin Microbiol Rev"},{"issue":"2","key":"ppat.1014640.ref002","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1089\/fpd.2019.2676","article-title":"The Epidemiology of Monophasic Salmonella Typhimurium","volume":"17","author":"H Sun","year":"2020","journal-title":"Foodborne Pathog Dis"},{"issue":"4","key":"ppat.1014640.ref003","doi-asserted-by":"crossref","first-page":"632","DOI":"10.4315\/0362-028X.JFP-16-331","article-title":"Foodborne salmonellosis in Italy: characterization of Salmonella 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