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Peer-reviewedCC BY 4.0Antimicrobial Agents and Chemotherapy

Penicillin-resistant Streptococcus dysgalactiae subsp. equisimilis and the association with penicillin-binding protein mutations: a population genotypic and phenotypic study

3 more authors
16 affiliations
  1. 1Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  2. 2Department of Infectious Diseases, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  3. 3Monash Infectious Diseases, Monash Health, Melbourne, Victoria, Australia
  4. 4Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia
  5. 5School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland, Australia
  6. 6Department of Infectious Diseases, Blacktown Hospital, Sydney, NSW, Australia
  7. 7Doherty Applied Microbial Genomics, Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  8. 8Department of Infectious Diseases, Westmead Hospital, Sydney, NSW, Australia
  9. 9Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
  10. 10NSW Health Pathology, Westmead Hospital, Sydney, NSW, Australia
  11. 11Victorian Infectious Diseases Service, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  12. 12Department of Microbiology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
  13. 13Centre for Inflammatory Diseases, Monash University, Melbourne, Victoria, Australia
  14. 14Infectious Diseases Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia
  15. 15Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney, NSW, Australia
  16. 16Department of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

Abstract

Streptococcus dysgalactiae subspecies equisimilis (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] ≥0.256 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 = 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 (2011–2023, 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 = 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.

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BibTeX
@article{xie2026penicillinresistant,
  title = {{Penicillin-resistant Streptococcus dysgalactiae subsp. equisimilis and the association with penicillin-binding protein mutations: a population genotypic and phenotypic study}},
  author = {Ouli Xie and Aimee Tan and Thanh Binh Nguyen and Andrew J. Hayes and Ravindra Dotel and Glen Carter and Matthew V. N. O'Sullivan and Katherine Bond and Christopher A. McDevitt and Tony M. Korman and Bart J. Currie and David B. Ascher and Steven Y. C. Tong and Sebastiaan J. van Hal and Mark R. Davies},
  journal = {Antimicrobial Agents and Chemotherapy},
  year = {2026},
  month = aug,
  doi = {10.1128/aac.00137-26},
  url = {https://doi.org/10.1128/aac.00137-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Penicillin-resistant Streptococcus dysgalactiae subsp. equisimilis and the association with penicillin-binding protein mutations: a population genotypic and phenotypic study
AU  - Ouli Xie
AU  - Aimee Tan
AU  - Thanh Binh Nguyen
AU  - Andrew J. Hayes
AU  - Ravindra Dotel
AU  - Glen Carter
AU  - Matthew V. N. O'Sullivan
AU  - Katherine Bond
AU  - Christopher A. McDevitt
AU  - Tony M. Korman
AU  - Bart J. Currie
AU  - David B. Ascher
AU  - Steven Y. C. Tong
AU  - Sebastiaan J. van Hal
AU  - Mark R. Davies
PY  - 2026
DA  - 2026/08/03
JO  - Antimicrobial Agents and Chemotherapy
DO  - 10.1128/aac.00137-26
UR  - https://doi.org/10.1128/aac.00137-26
AB  - Streptococcus dysgalactiae subspecies equisimilis (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] ≥0.256 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 = 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 (2011–2023, 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 = 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.
SN  - 0066-4804
SN  - 1098-6596
ER  -