Reduced Susceptibility of Streptococcus Pyogenes to β-Lactam Antibiotics Associated with Mutations in the Gene Is Geographically Widespread

Recently, two related strains with reduced susceptibility to ampicillin, amoxicillin, and cefotaxime, antibiotics commonly used to treat infections, were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the gene, encoding penicillin-binding protein 2X (PBP2X). This concerning report led us to investigate our library of 7,025 genome sequences of type , , and clinical strains recovered from intercontinental sources for mutations in We identified 137 strains that, combined, had 37 nonsynonymous mutations in 36 codons in Although to a lesser magnitude than the two previously published isolates, many of our strains had decreased susceptibility to multiple beta-lactam antibiotics. Many mutations were found only in single strains, but 16 groups of two or more isolates of the same type had an identical amino acid replacement. Phylogenetic analysis showed that, with one exception, strains of the same 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 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 gene subtypes. Enhanced surveillance and further epidemiological and molecular genetic study of this potential emergent antimicrobial problem are warranted.