{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:32:13Z","timestamp":1793133133348,"version":"4.5.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Avant Foundation Doctors in Training Research Scholarship","award":["2021\/000017"],"award-info":[{"award-number":["2021\/000017"]}],"id":[{"id":"https:\/\/ror.org\/02t23r064","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHMRC Investigator Grant","award":["GNT1174405, GNT2043549"],"award-info":[{"award-number":["GNT1174405, GNT2043549"]}]},{"name":"Australian National Health and Medical Research Council (NHMRC) postgraduate scholarship","award":["GNT2013831"],"award-info":[{"award-number":["GNT2013831"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Streptococcus dysgalactiae<\/jats:italic>\n                      subspecies\n                      <jats:italic toggle=\"yes\">equisimilis<\/jats:italic>\n                      (SDSE) is increasingly recognized as a cause of human disease. Despite decades of penicillin use, SDSE is near universally penicillin-susceptible. Here we report and characterize by whole genome sequencing (WGS) three penicillin-resistant SDSE isolates (minimum inhibitory concentration [MIC] \u22650.256 mg\/L) isolated from blood and skin in an individual with recurrent cellulitis on penicillin prophylaxis. The isolates carried 11 penicillin-binding protein (PBP) PBP2x, five PBP1a, and one PBP2b mutations that were distinct from the only previously reported WGS-characterized penicillin-resistant SDSE isolates (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 4). We then took a genotype-led approach to test the MICs of penicillin and amoxicillin for 63 isolates with PBP2x, PBP1a, and PBP2b variants selected from a well-characterized database of invasive SDSE isolates from Australia (2011\u20132023,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 436). PBPs were highly conserved in Australian invasive SDSE genomes. Only a single isolate carrying a PBP2x variant with five mutations around the penicillin-binding cleft found in 1\/436 invasive isolates demonstrated a four-fold rise in penicillin MIC, although remaining below clinical breakpoints. Strains with PBP2b and PBP1a variants alone were not associated with raised MICs. To provide broader context for PBP variants, we then examined a global database of SDSE genomes (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 1,160). PBP2x mutations in isolates with raised and\/or resistant penicillin MICs were found in only nine global SDSE database genomes. SDSE penicillin resistance is rare and associated with multiple PBP mutations, particularly PBP2x. WGS with phenotypic testing of novel PBP variants could be used to monitor emerging mutations associated with raised penicillin MICs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00137-26","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:28:06Z","timestamp":1785763686000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Penicillin-resistant\n                    <i>Streptococcus dysgalactiae<\/i>\n                    subsp.\n                    <i>equisimilis<\/i>\n                    and the association with penicillin-binding protein mutations: a population genotypic and phenotypic study"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5032-1932","authenticated-orcid":false,"given":"Ouli","family":"Xie","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, University of Melbourne, The Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"id":[{"id":"https:\/\/ror.org\/02t1bej08","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash Infectious Diseases, Monash Health","place":["Melbourne, Australia"]},{"id":[{"id":"https:\/\/ror.org\/048zcaj52","id-type":"ROR","asserted-by":"publisher"}],"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University","place":["Darwin, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7257-1051","authenticated-orcid":true,"given":"Aimee","family":"Tan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4150-5991","authenticated-orcid":false,"given":"Thanh Binh","family":"Nguyen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Chemistry and Molecular Biosciences, University of Queensland","place":["St Lucia, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Hayes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra","family":"Dotel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017bddy38","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Blacktown Hospital","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen","family":"Carter","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Doherty Applied Microbial Genomics, Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew V. N.","family":"O'Sullivan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gp5yv64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Westmead Hospital","place":["Sydney, Australia"]},{"id":[{"id":"https:\/\/ror.org\/0384j8v12","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculty of Medicine and Health, The University of Sydney","place":["Sydney, Australia"]},{"id":[{"id":"https:\/\/ror.org\/04gp5yv64","id-type":"ROR","asserted-by":"publisher"}],"name":"NSW Health Pathology, Westmead Hospital","place":["Sydney, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4473-9232","authenticated-orcid":true,"given":"Katherine","family":"Bond","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, University of Melbourne, The Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"id":[{"id":"https:\/\/ror.org\/016899r71","id-type":"ROR","asserted-by":"publisher"}],"name":"Victorian Infectious Diseases Service, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]},{"id":[{"id":"https:\/\/ror.org\/005bvs909","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, The Royal Melbourne Hospital","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1596-4841","authenticated-orcid":true,"given":"Christopher A.","family":"McDevitt","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ej9dk98","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6155-8353","authenticated-orcid":true,"given":"Tony M.","family":"Korman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02t1bej08","id-type":"ROR","asserted-by":"publisher"}],"name":"Monash Infectious Diseases, Monash Health","place":["Melbourne, Australia"]},{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Inflammatory Diseases, Monash University","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8878-8837","authenticated-orcid":false,"given":"Bart J.","family":"Currie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/048zcaj52","id-type":"ROR","asserted-by":"publisher"}],"name":"Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University","place":["Darwin, Australia"]},{"id":[{"id":"https:\/\/ror.org\/04jq72f57","id-type":"ROR","asserted-by":"publisher"}],"name":"Infectious Diseases Department, Royal Darwin Hospital","place":["Darwin, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-2413","authenticated-orcid":true,"given":"David B.","family":"Ascher","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Chemistry and Molecular Biosciences, University of Queensland","place":["St Lucia, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-8356","authenticated-orcid":true,"given":"Steven Y. 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