2019
DOI: 10.1093/cid/ciz1000
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Streptococcus pyogenes pbp2x Mutation Confers Reduced Susceptibility to β-Lactam Antibiotics

Abstract: Two near-identical clinical Streptococcus pyogenes isolates of emm subtype emm43.4 with a pbp2x missense mutation (T553K) were detected. Minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin were 8-fold higher, and the MIC for cefotaxime was 3-fold higher than for near-isogenic control isolates, consistent with a first step in developing β-lactam resistance.

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Cited by 84 publications
(89 citation statements)
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“…There were 105 unique amino acid sequence variants of the S. pyogenes PBP2x sequence with no major frameshifts or premature stop codons ( Supplementary File 1 ). We found no instances of the T553K substitution in the PBP2x KSGT motif as reported in the recent S. pyogenes β-lactam resistant isolates (2). Only four S. pyogenes isolate sequences (0.04%) had substitutions within the transpeptidase active site motifs of PBP2x ( Figure 1 and Table 1 ) corresponding to STMK to SAMK and STMK to STIK.…”
Section: Resultssupporting
confidence: 82%
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“…There were 105 unique amino acid sequence variants of the S. pyogenes PBP2x sequence with no major frameshifts or premature stop codons ( Supplementary File 1 ). We found no instances of the T553K substitution in the PBP2x KSGT motif as reported in the recent S. pyogenes β-lactam resistant isolates (2). Only four S. pyogenes isolate sequences (0.04%) had substitutions within the transpeptidase active site motifs of PBP2x ( Figure 1 and Table 1 ) corresponding to STMK to SAMK and STMK to STIK.…”
Section: Resultssupporting
confidence: 82%
“…Only four isolates contained mutations in the transpeptidase active sites of PBP2x and PBP1a. Although the report of two S. pyogenes isolates with reduced β-lactam susceptibility associated with pbp2x mutations is concerning (2), our findings provide reassurance that these are extremely limited, and perhaps unique, occurrences at this stage. We found a high degree of conservation of GAS PBP2x and PBP1a at transpeptidase active sites and across the broader transpeptidase domains.…”
Section: Discussionsupporting
confidence: 60%
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“…Beta-lactam antibiotics that inhibit peptidoglycan synthesis are the primary antibacterial treatment for S. pyogenes infections, and despite over 75 years of use, no penicillin-resistant clinical isolate has been reported (10, 11). However, two recent studies reporting reduced in vitro susceptibility to beta-lactam antibiotics among clinical isolates are of concern (12, 13). Macrolides are secondary alternative antibiotics recommended for individuals allergic to penicillin.…”
Section: Introductionmentioning
confidence: 99%