Diversity of penicillin-binding protein 2x in Streptococcus pyogenes from England and Wales, 2001 to 2015
- 1Imperial College London
Abstract
Streptococcus pyogenes remains clinically susceptible to {beta}-lactam antibiotics, its first-line treatment. Yet recent reports from the US, Iceland, and Japan have identified isolates with PBP2x (a primary {beta}-lactam target) substitutions that reduced antibiotic susceptibility. To determine whether these PBP2x substitutions occurred in S. pyogenes from England and Wales, we re-analysed 2,970 invasive genomes from 2001 to 2015. We found 42 PBP2x sequence mutants in 34% (996/2,970) of the genomes, revealing an unexpected diversity in this antibiotic target. Nine emm12 isolates carried a novel double substitution, PBP2x G600A_P601H, that co-occurred with macrolide resistance genes. Experimentally, these isolates showed 2- to 4-fold elevated minimum inhibitory concentrations for four {beta}-lactam antibiotics, alongside erythromycin resistance. Other PBP2x substitutions, found across seven emm types without reduced antibiotic susceptibility, appeared driven by emm lineage expansion rather than antibiotic pressure. These findings establish a baseline for pbp2x variation, reinforcing the case for sustained genomic surveillance globally.
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BibTeX
@misc{sveikauskaite2026diversity,
title = {{Diversity of penicillin-binding protein 2x in Streptococcus pyogenes from England and Wales, 2001 to 2015}},
author = {G. Sveikauskaite and A. L. Marshall and S. Gorshkova and R. L. Guy and Y. Wan and A. Vieira and J. Coelho and K. Moganeradj and S. Sriskandan and E. Jauneikaite and V. W. Soo},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.752073},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.752073v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Diversity of penicillin-binding protein 2x in Streptococcus pyogenes from England and Wales, 2001 to 2015
AU - G. Sveikauskaite
AU - A. L. Marshall
AU - S. Gorshkova
AU - R. L. Guy
AU - Y. Wan
AU - A. Vieira
AU - J. Coelho
AU - K. Moganeradj
AU - S. Sriskandan
AU - E. Jauneikaite
AU - V. W. Soo
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.752073
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.752073v1
AB - Streptococcus pyogenes remains clinically susceptible to {beta}-lactam antibiotics, its first-line treatment. Yet recent reports from the US, Iceland, and Japan have identified isolates with PBP2x (a primary {beta}-lactam target) substitutions that reduced antibiotic susceptibility. To determine whether these PBP2x substitutions occurred in S. pyogenes from England and Wales, we re-analysed 2,970 invasive genomes from 2001 to 2015. We found 42 PBP2x sequence mutants in 34% (996/2,970) of the genomes, revealing an unexpected diversity in this antibiotic target. Nine emm12 isolates carried a novel double substitution, PBP2x G600A_P601H, that co-occurred with macrolide resistance genes. Experimentally, these isolates showed 2- to 4-fold elevated minimum inhibitory concentrations for four {beta}-lactam antibiotics, alongside erythromycin resistance. Other PBP2x substitutions, found across seven emm types without reduced antibiotic susceptibility, appeared driven by emm lineage expansion rather than antibiotic pressure. These findings establish a baseline for pbp2x variation, reinforcing the case for sustained genomic surveillance globally.
ER -