Newswise \u2014 DALLAS \u2013\u00a0Feb.\u00a027, 2026 \u2013 Men are more susceptible than women to skin infections caused by\u00a0Staphylococcus aureus\u00a0bacteria, but the biological basis for this disparity has remained unclear. A new study led by UT\u00a0Southwestern Medical Center researchers is the first to reveal testosterone, present at higher levels in males, as a key driver of infection. The sex steroid activates a bacterial communication pathway known as quorum sensing, increasing skin cell death and promoting the destruction of red blood cells and white blood cells called neutrophils.\u00a0<\/p>\n
Published in\u00a0Nature Microbiology<\/a>,\u00a0the study also reported that a mirror-image form of testosterone, known as an\u00a0enantiomer\u00a0(ent-T), blocks quorum sensing and prevents\u00a0S. aureus\u00a0from damaging tissue in mice models. Senior author\u00a0Tamia Harris-Tryon, M.D., Ph.D.<\/a>, Associate Professor of\u00a0Dermatology<\/a>\u00a0and\u00a0Immunology<\/a>\u00a0at UT\u00a0Southwestern, and first author Maria S. John, Ph.D., a UTSW postdoctoral researcher,\u00a0have a patent pending for an\u00a0ent-T-based therapeutic along with collaborators at the University of Colorado.<\/p>\n \u201cThis research has important implications for treating\u00a0Staph\u00a0skin infections and conditions complicated by\u00a0Staphylococcus, such as atopic dermatitis, pemphigus, abscesses, and wound infections, including the deadliest skin infections caused by methicillin-resistant\u00a0Staphylococcus aureus\u00a0[MRSA],\u201d Dr. Harris-Tryon said. \u201cIt also explains why men are more susceptible to\u00a0Staph\u00a0infections.\u201d\u00a0<\/p>\n S. aureus\u00a0is the leading cause of skin infections. When it enters the bloodstream, it can cause septicemia, a life-threatening infection that may lead to organ failure.<\/p>\n During infection, the bacteria use quorum sensing to detect neighboring cells of the same species. As bacterial density rises, they produce short signaling molecules called auto-inducing peptides (AIP), which activate virulence programs and trigger toxin release, resulting in host-cell damage.\u00a0<\/p>\n The research team found that male skin cells consistently secrete higher levels of testosterone hormone than female skin cells. They also found the same is true for male mice, which were significantly more susceptible to\u00a0S. aureus\u00a0colonization and skin damage than female mice when exposed to a strain of MRSA. However, mice engineered to secrete less testosterone displayed greater resistance to the bacteria, while applying testosterone to the skin of female mice increased MRSA\u2019s severity.\u00a0<\/p>\n In laboratory experiments, testosterone activated quorum sensing even in the absence of AIPs. Other sex steroids, including progesterone and estrogen, had no measurable effect on quorum sensing.\u00a0<\/p>\n While using\u00a0ent-T as an experimental control, the researchers unexpectedly identified its therapeutic potential. In lab tests,\u00a0ent-T inhibited quorum sensing and reduced the bacteria\u2019s virulence. The molecule also inhibited quorum sensing on male and female mice when applied to their skin.\u00a0<\/p>\n Dr. Harris-Tryon won an Innovation Award from the UTSW\u00a0Office for Technology Development<\/a>\u00a0in 2024 to fund development of an\u00a0ent-T-based transdermal therapeutic for\u00a0Staph.<\/p>\n \u201cOur exciting finding suggests we can inhibit\u00a0S. aureus\u00a0virulence rather than killing the bacteria directly, an approach that prevents infection, preserves beneficial skin microbes, and reduces the selective pressure that drives antibiotic resistance while offering a potential new strategy to treat infections, including MRSA,\u201d Dr. John said.<\/p>\n This work builds on Dr. Harris-Tryon\u2019s studies in\u00a02023<\/a>\u00a0and\u00a02025<\/a>\u00a0with\u00a0Jeffrey McDonald, Ph.D.<\/a>, Professor in the\u00a0Center for Human Nutrition<\/a>\u00a0and of\u00a0Molecular Genetics<\/a>\u00a0at UTSW, that demonstrated sex-specific differences in skin hormone production. The team also has previously uncovered how the immune system\u00a0stimulates testosterone production<\/a>\u00a0in skin cells. Dr. Harris-Tryon said the current research builds on UT\u00a0Southwestern\u2019s longstanding leadership in steroid and skin hormone biology, a field in which the institution has been a global leader for decades.<\/p>\n A complete list of authors from UTSW can be found in the study.<\/p>\n Dr. Harris-Tryon holds the Thomas L. Shields, M.D. Professorship in Dermatology.<\/p>\n This research was funded by grants from the National Institutes of Health (NIAMS-K08AR076459, NIAID-AI162964, NIAID-AI153185, and NIAID-AI187273), the VA Merit Award (BX002711), and the Burroughs Wellcome Fund (1022777).<\/p>\n About UT\u00a0Southwestern Medical Center\u202f\u202f\u202f<\/p>\n UT\u00a0Southwestern, one of the nation\u2019s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution\u2019s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 25 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,300 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT\u00a0Southwestern physicians in more than 80 specialties care for more than 143,000 hospitalized patients, attend to more than 470,000 emergency room cases, and oversee nearly 5.3 million outpatient visits a year.<\/p>\n","protected":false},"excerpt":{"rendered":"Newswise \u2014 DALLAS \u2013\u00a0Feb.\u00a027, 2026 \u2013 Men are more susceptible than women to skin infections caused by\u00a0Staphylococcus aureus\u00a0bacteria,…\n","protected":false},"author":2,"featured_media":320368,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[1380,1698,103,396,61,2747,2757,60,1378,2361,144317,149142],"class_list":{"0":"post-320367","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-all-journal-news","9":"tag-dermatology","10":"tag-health","11":"tag-healthcare","12":"tag-ie","13":"tag-immunology","14":"tag-infectious-diseases","15":"tag-ireland","16":"tag-newswise","17":"tag-public-health","18":"tag-ut-southwestern-medical-center","19":"tag-ut-southwestern-medical-centerbasic-scienceinfectious-diseases-epidemiologyskintechnology-developmentcenter-for-human-nutritiondermatologytestosteroneimmunologymolecular-genetics"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/320367","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/comments?post=320367"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/posts\/320367\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media\/320368"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/media?parent=320367"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/categories?post=320367"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/ie\/wp-json\/wp\/v2\/tags?post=320367"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}