{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:36:02Z","timestamp":1788863762527,"version":"build-2803163510"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,6,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      is a leading cause of skin and soft tissue infections (SSTIs), which can escalate into systemic disease. While innate immune responses play a critical role in bacterial clearance, the bacterial components themselves can exacerbate inflammation. Here, we demonstrate that\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      lipoproteins (Lpp) and polymeric peptidoglycan (PG) synergistically induce skin abscesses in mice, in a process that requires both the lipid moiety of Lpp and the intact polymeric structure of PG. This synergy is mediated by Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and depends on infiltrating neutrophils and monocytes. Co-administration of Lpl1 and PG results in a 5-fold to 10-fold increase in macrophage inflammatory protein-2 (MIP-2) levels in the skin compared to either ligand alone, indicating a clear synergistic effect. Furthermore, we show that local alteration in coagulation and fibrinolysis contributes to the inflammatory response, as fibrinogen depletion significantly reduced lesion size. To extend these findings to a clinically relevant model, we employed an\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      double mutant that lacked both lipidation (\u0394\n                      <jats:italic toggle=\"yes\">lgt<\/jats:italic>\n                      ) and peptidoglycan O-acetyltransferase (\u0394\n                      <jats:italic toggle=\"yes\">oatA<\/jats:italic>\n                      ). This strain exhibited markedly attenuated virulence in a murine skin infection model. Importantly, this attenuation was fully reversed by neutrophil depletion, indicating that neutrophils are essential mediators of the host responses to these bacterial structures. Our findings reveal a cooperative mechanism through which\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      cell wall components drive skin lesion development, and we identify potential therapeutic targets for reducing the severity of SSTIs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      is a bacterium that often causes skin infections, including painful abscesses. We discovered that two components of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      , lipoproteins on its surface and peptidoglycan in its cell wall, collaborate to drive the formation of skin abscesses. This combination triggers potent immune responses by activating the receptor Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) on host cells. As a consequence, high numbers of neutrophils and monocytes swarm the infection site. The resulting immune overreaction, together with activation of the coagulation system, produces intense inflammation. We confirmed the importance of these bacterial components using mutant\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      strains in a skin infection model. These mutants generated much smaller abscesses in our experiments. Our findings highlight a cooperative mechanism that exacerbates staphylococcal infections. Targeting this synergy could be a valuable strategy to reduce disease severity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00840-26","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:00:18Z","timestamp":1778850018000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Staphylococcal lipoproteins and peptidoglycans synergize to drive skin abscess formation"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-2991","authenticated-orcid":true,"given":"Majd","family":"Mohammad","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01tm6cn81","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg","place":["Gothenburg, 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