{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:52:17Z","timestamp":1791474737835,"version":"4.3.4"},"reference-count":89,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"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":[[2024,11,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Streptococcus dysgalactiae<\/jats:italic>\n              subspecies\n              <jats:italic>equisimilis<\/jats:italic>\n              (SDSE) is a Gram-positive bacterial pathogen that infects humans and is closely related to group A streptococcus (GAS). Compared with GAS, far less is known about SDSE pathobiology. Increased rates of invasive SDSE infections have recently been reported in many countries. One SDSE\n              <jats:italic>emm<\/jats:italic>\n              type (\n              <jats:italic>stG62647<\/jats:italic>\n              ) is known to cause severe diseases, including necrotizing soft-tissue infections, endocarditis, and osteoarticular infections. To increase our understanding of the molecular pathogenesis of\n              <jats:italic>stG62647<\/jats:italic>\n              SDSE isolates causing human infections, we sequenced to closure the genomes of 120\n              <jats:italic>stG62647<\/jats:italic>\n              SDSE isolates. The genomes varied in size from 2.1 to 2.24 Mb pairs. The great majority of\n              <jats:italic>stG62647<\/jats:italic>\n              isolates had\n              <jats:italic>IS1548<\/jats:italic>\n              integrated into the\n              <jats:italic>silB<\/jats:italic>\n              gene, thereby inactivating it. Regions of difference, such as mobile genetic elements, were the largest source of genomic diversity. All 120\n              <jats:italic>stG62647<\/jats:italic>\n              isolates were assayed for virulence using a well-established mouse model of necrotizing myositis. An unexpectedly wide range of virulence was identified (20% to 95%), as assessed by near-mortality data. To explore the molecular mechanisms underlying virulence differences, we analyzed RNAseq transcriptome profiles for 38\n              <jats:italic>stG62647<\/jats:italic>\n              isolates (comprising the 19 least and most virulent) grown\n              <jats:italic>in vitro<\/jats:italic>\n              . Genetic polymorphisms were identified from whole-genome sequence data. Collectively, the results suggest that these SDSE isolates use multiple genetic pathways to alter virulence phenotype. The data also suggest that human genetics and underlying medical conditions contribute to disease severity. Our study integrates genomic, mouse virulence, and RNAseq data to advance our understanding of SDSE pathobiology and its molecular pathogenesis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              This study integrated genomic sequencing, mouse virulence assays, and bacterial transcriptomic analysis to advance our understanding of the molecular mechanisms contributing to\n              <jats:italic>Streptococcus dysgalactiae<\/jats:italic>\n              subsp.\n              <jats:italic>equisimilis emm<\/jats:italic>\n              type\n              <jats:italic>stG62647<\/jats:italic>\n              pathogenesis. We tested a large cohort of genetically closely related\n              <jats:italic>stG62647<\/jats:italic>\n              isolates for virulence using an established mouse model of necrotizing myositis and discovered a broad spectrum of virulence phenotypes, with near-mortality rates ranging from 20% to 95%. This variation was unexpected, given their close genetic proximity. Transcriptome analysis of\n              <jats:italic>stG62647<\/jats:italic>\n              isolates responsible for the lowest and highest near-mortality rates suggested that these isolates used multiple molecular pathways to alter their virulence. In addition, some genes encoding transcriptional regulators and putative virulence factors likely contribute to SDSE\n              <jats:italic>emm<\/jats:italic>\n              type\n              <jats:italic>stG62647<\/jats:italic>\n              pathogenesis. These data underscore the complexity of pathogen\u2013host interactions in an emerging SDSE clonal group.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02578-24","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T13:00:56Z","timestamp":1729170056000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Integrative genomic, virulence, and transcriptomic analysis of emergent\n            <i>Streptococcus dysgalactiae<\/i>\n            subspecies\n            <i>equisimilis<\/i>\n            (SDSE)\n            <i>emm<\/i>\n            type\n            <i>stG62647<\/i>\n            isolates causing human infections"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-8702","authenticated-orcid":true,"given":"Jesus M.","family":"Eraso","sequence":"first","affiliation":[{"name":"Laboratory for Molecular and Translational Human Infectious Diseases Research, Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA"},{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA"},{"name":"Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5295-4178","authenticated-orcid":false,"given":"Randall J.","family":"Olsen","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular and Translational Human Infectious Diseases Research, Center for Infectious Diseases, Houston Methodist Research Institute, Houston, Texas, USA"},{"name":"Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA"},{"name":"Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, USA"},{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3043-5307","authenticated-orcid":true,"given":"S. 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