Reduced in vitro susceptibility of Streptococcus pyogenes to beta-lactam antibiotics associated with mutations in the pbp2x gene is geographically widespread

Musser, J. M. et al. (2020) Reduced in vitro susceptibility of Streptococcus pyogenes to beta-lactam antibiotics associated with mutations in the pbp2x gene is geographically widespread. Journal of Clinical Microbiology, 58(4), e01993-19. (doi: 10.1128/JCM.01993-19) (PMID:31996443)

Abstract

Recently two related Streptococcus pyogenes strains with reduced susceptibility to ampicillin, amoxicillin and cefotaxime, antibiotics commonly used to treat S. pyogenes infections were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the pbp2x gene encoding penicillin-binding protein 2X (PBP2X). This concerning report led us to investigate our library of 7,025 genome sequences of type emm1, emm28, and emm89 S. pyogenes clinical strains recovered from intercontinental sources for mutations in pbp2x. We identified 137 strains that combined had 37 nonsynonymous mutations in 36 codons in pbp2x. Although to a lesser magnitude than the two previously published isolates, many of our strains had decreased susceptibility in vitro to multiple beta-lactam antibiotics. Many pbp2x mutations were found only in single strains, but 16 groups of two or more isolates of the same emm type had an identical amino acid replacement. Phylogenetic analysis showed that with one exception, strains of the same emm type with the same amino acid replacement were clonally related by descent. This finding indicates that strains with some amino acid changes in PBP2X can successfully spread to new human hosts and cause invasive infections. Mapping of the amino acid changes onto a three-dimensional structure of the related Streptococcus pneumoniae PBP2X suggests that some substitutions are located in regions functionally important in related pathogenic bacterial species. Decreased beta-lactam susceptibility is geographically widespread in strains of numerically common emm gene subtypes. Enhanced surveillance and further epidemiological and molecular genetic study of this potential emergent antimicrobial problem are warranted.

• Item Type: Articles
• Additional Information: This study was supported in part by the Fondren Foundation, Houston Methodist Hospital and Research Institute, and National Institutes of Health grants AI139369 and AI146771 (to J.M.M.), and AI32956 (to T.P.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Andrew
• Authors: Musser, J. M., Beres, S. B., Zhu, L., Olsen, R. J., Vuopio, J., Hyyryläinen, H.-L., Gröndahl-Yli-Hannuksela, K., Kristinsson, K. G., Darenberg, J., Henriques-Normark, B., Hoffmann, S., Caugant, D. A., Smith, A. J., Lindsay, D. S.J., Boragine, D., and Palzkill, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Journal of Clinical Microbiology
• Publisher: American Society for Microbiology
• ISSN: 0095-1137
• ISSN (Online): 1098-660X
• Published Online: 29 January 2020
• Copyright Holders: Copyright © 2020 American Society for Microbiology
• First Published: First published in Journal of Clinical Microbiology 58(4): e01993-19
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher