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Published on: September 11, 2020
Genetic heterogeneity in pbp genes among clinically isolated group B Streptococci with reduced penicillin
Noriyuki Nagano1, Yukiko Nagano, Kouji Kimura
1Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan. yarakawa@nih.go.jp.
Abstract:
The recent emergence of group B streptococcal isolates exhibiting increased penicillin MICs at the Funabashi Municipal Medical Center and other hospitals in Japan prompted a comparative analysis of the penicillin-binding proteins (PBPs) from those strains with the PBPs from penicillin-susceptible strains comprising four neonatal invasive strains isolated from 1976 to 1988 and two recent isolates. The PBP sequences of the penicillin-susceptible strains were highly conserved, irrespective of their isolation date. Of six strains with reduced susceptibility to penicillin (penicillin MICs, 0.25 to 0.5 mug/ml), strains R1, R2, R5, and R6 shared a unique set of five amino acid substitutions, including V405A adjacent to the (402)SSN(404) motif in PBP 2X and one in PBP 2B. The remaining two strains, R3 and R4, shared several substitutions, including Q557E adjacent to the (552)KSG(554) motif in PBP 2X, in addition to the substitutions in PBP 2B, which are commonly found among penicillin-insusceptible strains. Strains R7 and R8, which had a penicillin MIC of 1 mug/ml, shared a unique set of eight amino acid substitutions (two in PBP 2X; two in PBP 2B, including G613R adjacent to the (614)KTG(616) motif; three in PBP 1A; and one in PBP 2A), and the Q557E substitution in PBP 2X was common to R3 and R4. The binding of Bocillin FL was reduced or not detected in some PBPs, including PBP 2X of penicillin-insusceptible strains, but no significant reduction in the level of pbp2x transcription was found in such strains. The results of phylogenetic comparative analyses imply the absence of epidemic penicillin-insusceptible strains, and several genetic lineages of penicillin-insusceptible strains have been independently emerging through the accumulation of mutations in their pbp genes, especially in pbp2x.
Insights
Group B Streptococcus strains show increasing penicillin resistance due to mutations in penicillin-binding proteins (PBPs), particularly PBP 2X. These genetic changes suggest independent emergence rather than epidemic spread of resistant strains.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Group B Streptococcus (GBS) is a significant cause of neonatal infections.
- Emergence of GBS isolates with increased penicillin minimum inhibitory concentrations (MICs) has been observed.
- Penicillin-binding proteins (PBPs) are crucial targets for beta-lactam antibiotics.
Purpose of the Study:
- To comparatively analyze penicillin-binding proteins (PBPs) in penicillin-susceptible and resistant Group B Streptococcus strains.
- To investigate the genetic basis of reduced penicillin susceptibility in GBS.
Main Methods:
- Comparative analysis of PBP sequences from susceptible and resistant GBS isolates.
- Identification of amino acid substitutions in PBPs, especially PBP 2X and PBP 2B.
- Assessment of Bocillin FL binding to PBPs.
- Analysis of pbp2x gene transcription levels.
Main Results:
- Penicillin-susceptible GBS strains showed highly conserved PBP sequences.
- Resistant strains exhibited unique sets of amino acid substitutions in PBP 2X and PBP 2B.
- Reduced Bocillin FL binding was observed in PBPs of some resistant strains, notably PBP 2X.
- No significant reduction in pbp2x transcription was detected in resistant strains.
Conclusions:
- Multiple, independent genetic lineages of penicillin-resistant GBS are emerging.
- Accumulation of mutations in PBP genes, particularly pbp2x, drives penicillin resistance.
- The findings suggest an absence of epidemic penicillin-resistant GBS strains.
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