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A novel integrative and conjugative element in Streptococcus pyogenes carries a cfr-like gene associated with linezolid resistance in other species.

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Τίτλος: A novel integrative and conjugative element in Streptococcus pyogenes carries a cfr-like gene associated with linezolid resistance in other species.
Συγγραφείς: Amusin DB; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Simons LM; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Garcia DS; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Hauser AR; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Office E; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Jaggi P; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA., Williams DB; Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Kociolek LK; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Patel AB; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Shulman ST; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Guzman-Cottrill JA; Department of Pediatrics, Division of Infectious Diseases, Oregon Health & Science University Doernbecher Children's Hospital, Portland, Oregon, USA., Tanz RR; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Advanced General Pediatrics & Primary Care, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Ozer EA; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Πηγή: MSphere [mSphere] 2026 Sep 29; Vol. 11 (9), pp. e0027726. Date of Electronic Publication: 2026 Aug 21.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101674533 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2379-5042 (Electronic) Linking ISSN: 23795042 NLM ISO Abbreviation: mSphere Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, DC : American Society for Microbiology, [2015]-
Ιατρικοί όροι (MeSH): Streptococcus pyogenes*/genetics , Streptococcus pyogenes*/drug effects , Streptococcus pyogenes*/isolation & purification , Linezolid*/pharmacology , Anti-Bacterial Agents*/pharmacology , Drug Resistance, Multiple, Bacterial*/genetics , Bacterial Proteins*/genetics , Interspersed Repetitive Sequences*, Streptococcal Infections/microbiology ; Pharyngitis/microbiology ; Clindamycin/pharmacology ; Humans ; Microbial Sensitivity Tests ; Whole Genome Sequencing ; Conjugation, Genetic
Περίληψη: Treatment of severe invasive Streptococcus pyogenes infections has historically relied on β-lactam antibiotics with adjunctive clindamycin. Rising rates of lincosamide resistance have led to adoption of linezolid as an alternative adjunctive therapy. This report describes a clinical S. pyogenes isolate carrying a multi-drug resistance gene, cfr(C), known to confer the phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPSA) resistance phenotype in other bacterial species. Strain GAS-390756 is a pharyngeal isolate collected from a child with pharyngitis in the United States. Whole-genome sequence analysis demonstrated that the isolate belonged to emm type 89 and carried an integrative and conjugative element with erm(B) and cfr(C) cargo genes (ICESpy390756). Antimicrobial susceptibility testing demonstrated the isolate was resistant to erythromycin and clindamycin but susceptible to linezolid, consistent with the activity of erm(B) but not cfr(C). Comparative analysis of cfr(C)'s genomic context suggested that the promoter sequence may have been lost during ICESpy390756's acquisition of the gene. While GAS-390756 remains susceptible to linezolid, the expansion of cfr(C)'s host range into S. pyogenes and its presence on a novel mobile element are concerning. In light of known expression mechanisms for other silent antimicrobial resistance genes, this observation carries epidemiologic and public health importance.
Importance: Treatment of severe invasive Streptococcus pyogenes infection has traditionally relied on the adjunctive use of clindamycin with β-lactam antibiotic therapy. However, rising rates of clindamycin non-susceptibility have led clinicians to adopt linezolid as an alternative therapy. We identified S. pyogenes isolated from a child with pharyngitis that carried the cfr(C) gene. This gene causes resistance to multiple antibiotics, including clindamycin and linezolid, in other bacterial species. At the time of this study, we found no other instances of the cfr(C) gene carried by S. pyogenes in either published reports or the public genome sequence database. While this isolate remained sensitive to linezolid, the expanded host range of cfr(C) found in a novel potentially mobile genomic element may herald the eventual emergence of broader antibiotic resistance in S. pyogenes.
Competing Interests: The authors declare no conflict of interest.
References: JAMA. 2025 May 6;333(17):1498-1507. (PMID: 40193120)
Clin Microbiol Rev. 2021 Jun 16;34(3):e0018820. (PMID: 34076490)
J Antimicrob Chemother. 2021 Nov 12;76(12):3310-3312. (PMID: 34510186)
Antimicrob Agents Chemother. 2006 Jul;50(7):2500-5. (PMID: 16801432)
Sci Rep. 2021 Jun 16;11(1):12728. (PMID: 34135355)
J Antimicrob Chemother. 2018 Jul 1;73(7):1880-1887. (PMID: 29659858)
Open Forum Infect Dis. 2023 Nov 24;10(12):ofad588. (PMID: 38149106)
Lancet Infect Dis. 2021 May;21(5):697-710. (PMID: 33333013)
Nucleic Acids Res. 2021 Jan 8;49(D1):D1020-D1028. (PMID: 33270901)
Bioinformatics. 2008 Aug 15;24(16):1757-64. (PMID: 18567917)
Lancet Infect Dis. 2025 Mar;25(3):265-275. (PMID: 39396526)
Antimicrob Agents Chemother. 2017 Jun 27;61(7):. (PMID: 28483950)
Int J Antimicrob Agents. 2017 Sep;50(3):496-500. (PMID: 28663118)
J Antimicrob Chemother. 2017 Jun 1;72(6):1581-1588. (PMID: 28186558)
J Antimicrob Chemother. 2023 Mar 2;78(3):586-598. (PMID: 36719135)
Int J Med Microbiol. 2022 Aug;312(6):151559. (PMID: 35961233)
Grant Information: T32GM144295 United States NH NIH HHS; BAA 75D301-19C-06841 United States JG JG CDC HHS; BAA 75D301-22-R-72097 United States JG JG CDC HHS; S10 OD032243 United States NH NIH HHS
Contributed Indexing: Keywords: Group A streptococcus; Streptococcus pyogenes; cfr; linezolid; oxazolidinones
Substance Nomenclature: ISQ9I6J12J (Linezolid)
0 (Anti-Bacterial Agents)
3U02EL437C (Clindamycin)
0 (Bacterial Proteins)
Entry Date(s): Date Created: 20260821 Date Completed: 20260929 Latest Revision: 20261001
Update Code: 20261001
PubMed Central ID: PMC13621865
DOI: 10.1128/msphere.00277-26
PMID: 42627159
Βάση Δεδομένων: MEDLINE
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  Data: A novel integrative and conjugative element in Streptococcus pyogenes carries a cfr-like gene associated with linezolid resistance in other species.
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  Data: <searchLink fieldCode="AU" term="%22Amusin+DB%22">Amusin DB</searchLink>; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Simons+LM%22">Simons LM</searchLink>; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Garcia+DS%22">Garcia DS</searchLink>; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Hauser+AR%22">Hauser AR</searchLink>; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Office+E%22">Office E</searchLink>; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Jaggi+P%22">Jaggi P</searchLink>; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.<br /><searchLink fieldCode="AU" term="%22Williams+DB%22">Williams DB</searchLink>; Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Kociolek+LK%22">Kociolek LK</searchLink>; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Patel+AB%22">Patel AB</searchLink>; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Shulman+ST%22">Shulman ST</searchLink>; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Guzman-Cottrill+JA%22">Guzman-Cottrill JA</searchLink>; Department of Pediatrics, Division of Infectious Diseases, Oregon Health & Science University Doernbecher Children's Hospital, Portland, Oregon, USA.<br /><searchLink fieldCode="AU" term="%22Tanz+RR%22">Tanz RR</searchLink>; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Division of Advanced General Pediatrics & Primary Care, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.<br /><searchLink fieldCode="AU" term="%22Ozer+EA%22">Ozer EA</searchLink>; Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
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  Data: Treatment of severe invasive Streptococcus pyogenes infections has historically relied on β-lactam antibiotics with adjunctive clindamycin. Rising rates of lincosamide resistance have led to adoption of linezolid as an alternative adjunctive therapy. This report describes a clinical S. pyogenes isolate carrying a multi-drug resistance gene, cfr(C), known to confer the phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPS<subscript>A</subscript>) resistance phenotype in other bacterial species. Strain GAS-390756 is a pharyngeal isolate collected from a child with pharyngitis in the United States. Whole-genome sequence analysis demonstrated that the isolate belonged to emm type 89 and carried an integrative and conjugative element with erm(B) and cfr(C) cargo genes (ICESpy390756). Antimicrobial susceptibility testing demonstrated the isolate was resistant to erythromycin and clindamycin but susceptible to linezolid, consistent with the activity of erm(B) but not cfr(C). Comparative analysis of cfr(C)'s genomic context suggested that the promoter sequence may have been lost during ICESpy390756's acquisition of the gene. While GAS-390756 remains susceptible to linezolid, the expansion of cfr(C)'s host range into S. pyogenes and its presence on a novel mobile element are concerning. In light of known expression mechanisms for other silent antimicrobial resistance genes, this observation carries epidemiologic and public health importance.<br />Importance: Treatment of severe invasive Streptococcus pyogenes infection has traditionally relied on the adjunctive use of clindamycin with β-lactam antibiotic therapy. However, rising rates of clindamycin non-susceptibility have led clinicians to adopt linezolid as an alternative therapy. We identified S. pyogenes isolated from a child with pharyngitis that carried the cfr(C) gene. This gene causes resistance to multiple antibiotics, including clindamycin and linezolid, in other bacterial species. At the time of this study, we found no other instances of the cfr(C) gene carried by S. pyogenes in either published reports or the public genome sequence database. While this isolate remained sensitive to linezolid, the expanded host range of cfr(C) found in a novel potentially mobile genomic element may herald the eventual emergence of broader antibiotic resistance in S. pyogenes.
– Name: Abstract
  Label: Competing Interests
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  Data: The authors declare no conflict of interest.
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  Label: References
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  Data: JAMA. 2025 May 6;333(17):1498-1507. (PMID: <searchLink fieldCode="PM" term="%2240193120%22">40193120)</searchLink><br />Clin Microbiol Rev. 2021 Jun 16;34(3):e0018820. (PMID: <searchLink fieldCode="PM" term="%2234076490%22">34076490)</searchLink><br />J Antimicrob Chemother. 2021 Nov 12;76(12):3310-3312. (PMID: <searchLink fieldCode="PM" term="%2234510186%22">34510186)</searchLink><br />Antimicrob Agents Chemother. 2006 Jul;50(7):2500-5. (PMID: <searchLink fieldCode="PM" term="%2216801432%22">16801432)</searchLink><br />Sci Rep. 2021 Jun 16;11(1):12728. (PMID: <searchLink fieldCode="PM" term="%2234135355%22">34135355)</searchLink><br />J Antimicrob Chemother. 2018 Jul 1;73(7):1880-1887. (PMID: <searchLink fieldCode="PM" term="%2229659858%22">29659858)</searchLink><br />Open Forum Infect Dis. 2023 Nov 24;10(12):ofad588. (PMID: <searchLink fieldCode="PM" term="%2238149106%22">38149106)</searchLink><br />Lancet Infect Dis. 2021 May;21(5):697-710. (PMID: <searchLink fieldCode="PM" term="%2233333013%22">33333013)</searchLink><br />Nucleic Acids Res. 2021 Jan 8;49(D1):D1020-D1028. (PMID: <searchLink fieldCode="PM" term="%2233270901%22">33270901)</searchLink><br />Bioinformatics. 2008 Aug 15;24(16):1757-64. (PMID: <searchLink fieldCode="PM" term="%2218567917%22">18567917)</searchLink><br />Lancet Infect Dis. 2025 Mar;25(3):265-275. (PMID: <searchLink fieldCode="PM" term="%2239396526%22">39396526)</searchLink><br />Antimicrob Agents Chemother. 2017 Jun 27;61(7):. (PMID: <searchLink fieldCode="PM" term="%2228483950%22">28483950)</searchLink><br />Int J Antimicrob Agents. 2017 Sep;50(3):496-500. (PMID: <searchLink fieldCode="PM" term="%2228663118%22">28663118)</searchLink><br />J Antimicrob Chemother. 2017 Jun 1;72(6):1581-1588. (PMID: <searchLink fieldCode="PM" term="%2228186558%22">28186558)</searchLink><br />J Antimicrob Chemother. 2023 Mar 2;78(3):586-598. (PMID: <searchLink fieldCode="PM" term="%2236719135%22">36719135)</searchLink><br />Int J Med Microbiol. 2022 Aug;312(6):151559. (PMID: <searchLink fieldCode="PM" term="%2235961233%22">35961233)</searchLink>
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  Data: T32GM144295 United States NH NIH HHS; BAA 75D301-19C-06841 United States JG JG CDC HHS; BAA 75D301-22-R-72097 United States JG JG CDC HHS; S10 OD032243 United States NH NIH HHS
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  Data: <i>Keywords: </i>Group A streptococcus; Streptococcus pyogenes; cfr; linezolid; oxazolidinones
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      – SubjectFull: Streptococcal Infections microbiology
        Type: general
      – SubjectFull: Pharyngitis microbiology
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      – SubjectFull: Clindamycin pharmacology
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      – TitleFull: A novel integrative and conjugative element in Streptococcus pyogenes carries a cfr-like gene associated with linezolid resistance in other species.
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            – Type: issue
              Value: 9
          Titles:
            – TitleFull: MSphere
              Type: main
ResultId 1