{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:51:02Z","timestamp":1791399062635,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014644","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32573436"],"award-info":[{"award-number":["32573436"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U24A20453"],"award-info":[{"award-number":["U24A20453"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273059"],"award-info":[{"award-number":["32273059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32503106"],"award-info":[{"award-number":["32503106"]}],"id":[{"id":"10.13039\/501100001809","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                    (\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ), a major pathogen of mastitis, employs a diverse arsenal of virulence factors to invade and disrupt mammary tissues, thereby eliciting a complex and dysregulated inflammatory response. Sphingomyelin phosphodiesterase (Sph) has emerged as a key virulence determinant of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ; however, its potential role and underlying mechanisms in mastitis remain elusive. In this study, we demonstrate that Sph deficiency significantly suppresses\n                    <jats:italic>S. aureus<\/jats:italic>\n                    -induced ferroptosis. Mechanistically, Sph disrupts mitochondrial cristae through interaction with Mic60, a core component of the mitochondrial contact site and cristae-organizing system (MICOS). Sph-mediated cytosolic mitochondrial DNA (mtDNA) released is sensed by cyclic GMP-AMP synthase (cGAS), leading to activation of the STING signaling pathway, which further triggers the recruitment of GPX4 into the autophagy-lysosome pathway for degradation. Collectively, our study unveils a novel pathogenic mechanism whereby the\n                    <jats:italic>S. aureus<\/jats:italic>\n                    virulence factor Sph perturbs mitochondrial homeostasis, and engages the cGAS-STING axis to promote GPX4 degradation and ferroptosis, highlighting Sph as a potential therapeutic target for\n                    <jats:italic>S. aureus<\/jats:italic>\n                    -associated mastitis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014644","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:32:10Z","timestamp":1790703130000},"page":"e1014644","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sph-mediated mtDNA release and autophagy-dependent ferroptosis contribute to Staphylococcus aureus-induced mastitis"],"prefix":"10.1371","volume":"22","author":[{"given":"Yunfei","family":"Wei","sequence":"first","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Yin","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Zhai","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baihe","family":"Zhan","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeling","family":"Wang","sequence":"additional","affiliation":[{"name":"First Hospital, Jilin University","place":["Changchun, China"],"department":["Departments of Cardiovascular Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiakang","family":"He","sequence":"additional","affiliation":[{"name":"Guangxi University","place":["Nanning, Guangxi, China"],"department":["College of Animal Science and Technology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuming","family":"Deng","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-689X","authenticated-orcid":true,"given":"Haihua","family":"Feng","sequence":"additional","affiliation":[{"name":"Jilin University","place":["Changchun, China"],"department":["State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary 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