{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:06:30Z","timestamp":1789589190260,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Diabetes mellitus is a widespread chronic condition that can lead to a variety of complications. Among the numerous complications associated with diabetes, diabetic foot ulcers are particularly notable due to their high prevalence and potential severity. These ulcers are characterized by a substantial incidence rate, a considerable risk of infection, and a high probability of necessitating amputation.\n Staphylococcus aureus<\/jats:italic>\n , a notorious pathogen within this context, exacerbates wound pathogenesis and can facilitate ulcer extension and, in severe instances, gangrene through the secretion of numerous virulence factors.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n RT\u2013qPCR was used to analyze the expression of\n Staphylococcus aureus<\/jats:italic>\n adhesin virulence factors. Utilizing gene knockout techniques to deleted the\n sdrH<\/jats:italic>\n and\n icaA-C<\/jats:italic>\n genes. Biofilm formation of S. aureus was observed by scanning electron microscope. The effect of\n sdrH<\/jats:italic>\n and\n icaA-C<\/jats:italic>\n genes on\n S. aureus<\/jats:italic>\n infected wound healing was also evaluated using a diabetic mice skin wound infection model.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The\n sdrH<\/jats:italic>\n gene and the\n icaA-C<\/jats:italic>\n gene cluster are critical contributors to\n Staphylococcus aureus<\/jats:italic>\n infection in diabetic wounds. Post-infection with the\n sdrH<\/jats:italic>\n single-gene knockout strain, a significant enhancement in wound healing rates was observed, accompanied by a marked reduction in bacterial colonization per unit area. Conversely, no significant differences were detected between the\n icaA-C<\/jats:italic>\n gene cluster knockout strain and the wild-type strain. Compared to infections caused by either the wild-type strain or the\n sdrH<\/jats:italic>\n single-knockout strain, infection with the\n icaA-C<\/jats:italic>\n \/\n sdrH<\/jats:italic>\n double-knockout strain led to a marked increase in the wound healing rate and a significant reduction in bacterial load.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n This study presented that the\n sdrH<\/jats:italic>\n gene enhances the virulence of\n Staphylococcus aureus<\/jats:italic>\n in diabetic wounds by attenuating the host immune response, reducing the infiltration of inflammatory cells, and impairing the immune system\u2019s capacity to clear bacteria, thereby impeding the wound healing process. Although\n icaA-C<\/jats:italic>\n is not a pivotal player, it seems to enhance the virulence capabilities of\n sdrH<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1502428","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T01:30:03Z","timestamp":1750296603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["sdrH enhances Staphylococcus aureus infection in diabetic wounds"],"prefix":"10.3389","volume":"16","author":[{"given":"Kaiyu","family":"Nie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmei","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s12020-012-9619-x","article-title":"Diagnostics and treatment of the diabetic foot","volume":"41","author":"Apelqvist","year":"2012","journal-title":"Endocrine"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"445","DOI":"10.4161\/viru.2.5.17724","article-title":"Staphylococcus aureus biofilms: properties, regulation, and roles in human disease","volume":"2","author":"Archer","year":"2011","journal-title":"Virulence"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3389\/fcimb.2015.00007","article-title":"Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects","volume":"5","author":"Arciola","year":"2015","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1128\/JB.01000-07","article-title":"Genome sequence of Staphylococcus aureus strain Newman and comparative analysis of staphylococcal genomes: polymorphism and evolution of two major pathogenicity islands","volume":"190","author":"Baba","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1007\/s12325-014-0140-x","article-title":"Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights","volume":"31","author":"Baltzis","year":"2014","journal-title":"Adv. Ther."},{"key":"ref6","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/B978-0-12-809671-0.00002-4","article-title":"Chapter 2\u2014Pathogenesis of Staphylococcus aureus","volume-title":"Staphylococcus aureus","author":"Becker","year":"2018"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0378-1097(97)00116-X","article-title":"Gene replacement in Staphylococcus carnosus and Staphylococcus xylosus","volume":"151","author":"Br\u00fcckner","year":"1997","journal-title":"FEMS Microbiol. Lett."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/nchembio.2003","article-title":"Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence","volume":"12","author":"Chen","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"5427","DOI":"10.1128\/IAI.67.10.5427-5433.1999","article-title":"The intercellular adhesion (Ica) locus is present in Staphylococcus aureus and is required for biofilm formation","volume":"67","author":"Cramton","year":"1999","journal-title":"Infect. Immun."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1128\/CMR.00081-09","article-title":"Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic","volume":"23","author":"David","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1099\/00221287-6-1-2-95","article-title":"Staphylococcal coagulase; mode of action and antigenicity","volume":"6","author":"Duthie","year":"1952","journal-title":"J. Gen. Microbiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/j.1524-475X.2011.00681.x","article-title":"Quantitative analysis of the cellular inflammatory response against biofilm bacteria in chronic wounds","volume":"19","author":"Fazli","year":"2011","journal-title":"Wound Repair Regen."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.3389\/fmicb.2016.01601","article-title":"Molecular events for promotion of vancomycin resistance in vancomycin intermediate Staphylococcus aureus","volume":"7","author":"Hu","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1107\/S2059798321010068","article-title":"Structural basis for SdgB- and SdgA-mediated glycosylation of staphylococcal adhesive proteins","volume":"77","author":"Kim","year":"2021","journal-title":"Acta Crystallogr. D. Struct. Biol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"13552","DOI":"10.1038\/s41598-020-70666-y","article-title":"Effect of manuka honey on biofilm-associated genes expression during methicillin-resistant Staphylococcus aureus biofilm formation","volume":"10","author":"Kot","year":"2020","journal-title":"Sci. Rep."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1111\/apm.12295","article-title":"Surface proteins of Staphylococcus aureus play an important role in experimental skin infection","volume":"122","author":"Kwiecinski","year":"2014","journal-title":"APMIS"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"m997","DOI":"10.1136\/bmj.m997","article-title":"Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study","volume":"369","author":"Li","year":"2020","journal-title":"BMJ"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1186\/s12879-021-06516-7","article-title":"The microbiology of diabetic foot infections: a meta-analysis","volume":"21","author":"Macdonald","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e1002307","DOI":"10.1371\/journal.ppat.1002307","article-title":"Preventing Staphylococcus aureus sepsis through the inhibition of its agglutination in blood","volume":"7","author":"McAdow","year":"2011","journal-title":"PLoS Pathog."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1099\/00221287-146-7-1535","article-title":"The serine-aspartate repeat (Sdr) protein family in Staphylococcus epidermidis","volume":"146","author":"McCrea","year":"2000","journal-title":"Microbiology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1111\/j.1524-475X.2007.00273.x","article-title":"db\/db mice exhibit severe wound-healing impairments compared with other murine diabetic strains in a silicone-splinted excisional wound model","volume":"15","author":"Michaels","year":"2007","journal-title":"Wound Repair Regen."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"Unit 9C.1","DOI":"10.1002\/9780471729259.mc09c01s28","article-title":"Growth and laboratory maintenance of Staphylococcus aureus","volume":"28","author":"Missiakas","year":"2013","journal-title":"Curr. Protoc. Microbiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1021\/pr200029r","article-title":"Exoproteome of Staphylococcus aureus reveals putative determinants of nasal carriage","volume":"10","author":"Muthukrishnan","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1128\/IAI.00976-08","article-title":"Defects in innate immunity predispose C57BL\/6J-Leprdb\/Leprdb mice to infection by Staphylococcus aureus","volume":"77","author":"Park","year":"2009","journal-title":"Infect. Immun."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/j.1524-475X.2009.00489.x","article-title":"Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model","volume":"17","author":"Schierle","year":"2009","journal-title":"Wound Repair Regen."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.clindermatol.2010.03.009","article-title":"Chronic wound infection: facts and controversies","volume":"28","author":"Siddiqui","year":"2010","journal-title":"Clin. Dermatol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1073\/pnas.1716580115","article-title":"Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria","volume":"115","author":"V\u00e5gesj\u00f6","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"936","DOI":"10.3855\/jidc.5882","article-title":"Prevalence and antibiotic susceptibility of bacteria from acute and chronic wounds in Malaysian subjects","volume":"9","author":"Wong","year":"2015","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.imlet.2013.01.004","article-title":"Staphylococcus aureus virulence factors in evasion from innate immune defenses in human and animal diseases","volume":"150","author":"Zecconi","year":"2013","journal-title":"Immunol. Lett."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1080\/07853890.2016.1231932","article-title":"Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis (\u2020)","volume":"49","author":"Zhang","year":"2017","journal-title":"Ann. Med."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1502428\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T01:30:03Z","timestamp":1750296603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1502428\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,19]]},"references-count":31,"alternative-id":["10.3389\/fmicb.2025.1502428"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1502428","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,19]]},"article-number":"1502428"}}