A Single Amino Acid Replacement in Penicillin-Binding Protein 2X in Streptococcus pyogenes Significantly Increases Fitness on Subtherapeutic Benzylpenicillin Treatment in a Mouse Model of Necrotizing Myositis

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Invasive strains of Streptococcus pyogenes with significantly reduced susceptibility to β-lactam antibiotics have been recently described. These reports have caused considerable concern in the international infectious disease, medical microbiology, and public health communities because S. pyogenes has remained universally susceptible to β-lactam antibiotics for 70 years. Virtually all analyzed strains had single amino acid replacements in penicillin-binding protein 2X (PBP2X), a major target of β-lactam antibiotics in pathogenic bacteria. We used isogenic strains to test the hypothesis that a single amino acid replacement in PBP2X conferred a fitness advantage in a mouse model of necrotizing myositis. We determined that when mice were administered intermittent subtherapeutic dosing of benzylpenicillin, the strain with a Pro601Leu amino acid replacement in PBP2X that confers reduced β-lactam susceptibility in vitro was more fit, as assessed by the magnitude of colony-forming units recovered from disease tissue. These data provide important pathogenesis information that bears on this emerging global infectious disease problem.

Original languageEnglish (US)
Pages (from-to)1625-1631
Number of pages7
JournalAmerican Journal of Pathology
Volume190
Issue number8
DOIs
StatePublished - Aug 2020

Keywords

  • Amino Acid Substitution
  • Animals
  • Anti-Bacterial Agents/therapeutic use
  • Disease Models, Animal
  • Fasciitis, Necrotizing/drug therapy
  • Mice
  • Myositis/drug therapy
  • Penicillin G/therapeutic use
  • Penicillin-Binding Proteins/genetics
  • Streptococcus pyogenes/genetics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'A Single Amino Acid Replacement in Penicillin-Binding Protein 2X in Streptococcus pyogenes Significantly Increases Fitness on Subtherapeutic Benzylpenicillin Treatment in a Mouse Model of Necrotizing Myositis'. Together they form a unique fingerprint.

Cite this