Insight into the Diversity of Penicillin-Binding Protein 2x Alleles and Mutations in Viridans Streptococci

Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02646-16. doi: 10.1128/AAC.02646-16. Print 2017 May.

Abstract

The identification of commensal streptococci species is an everlasting problem due to their ability to genetically transform. A new challenge in this respect is the recent description of Streptococcus pseudopneumoniae as a new species, which was distinguished from closely related pathogenic S. pneumoniae and commensal S. mitis by a variety of physiological and molecular biological tests. Forty-one atypical S. pneumoniae isolates have been collected at the German National Reference Center for Streptococci (GNRCS). Multilocus sequence typing (MLST) confirmed 35 isolates as the species S. pseudopneumoniae A comparison with the pbp2x sequences from 120 commensal streptococci isolated from different continents revealed that pbp2x is distinct among penicillin-susceptible S. pseudopneumoniae isolates. Four penicillin-binding protein x (PBPx) alleles of penicillin-sensitive S. mitis account for most of the diverse sequence blocks in resistant S. pseudopneumoniae, S. pneumoniae, and S. mitis, and S. infantis and S. oralis sequences were found in S. pneumoniae from Japan. PBP2x genes of the family of mosaic genes related to pbp2x in the S. pneumoniae clone Spain23F-1 were observed in S. oralis and S. infantis as well, confirming its global distribution. Thirty-eight sites were altered within the PBP2x transpeptidase domains of penicillin-resistant strains, excluding another 37 sites present in the reference genes of sensitive strains. Specific mutational patterns were detected depending on the parental sequence blocks, in agreement with distinct mutational pathways during the development of beta-lactam resistance. The majority of the mutations clustered around the active site, whereas others are likely to affect stability or interactions with the C-terminal domain or partner proteins.

Keywords: PBP2x; PBP2x mutation; S. pseudopneumoniae; penicillin resistance; viridans streptococci.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Catalytic Domain / genetics
  • DNA, Bacterial / genetics
  • Genetic Variation / genetics
  • Genome, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Multilocus Sequence Typing
  • Mutation / genetics
  • Penicillin Resistance / genetics*
  • Penicillin-Binding Proteins / genetics*
  • Streptococcal Infections / drug therapy
  • Streptococcal Infections / pathology
  • Streptococcus pneumoniae / genetics*
  • Streptococcus pneumoniae / isolation & purification
  • Viridans Streptococci / classification*
  • Viridans Streptococci / genetics*
  • Viridans Streptococci / isolation & purification

Substances

  • DNA, Bacterial
  • Penicillin-Binding Proteins
  • PBP 2x protein, Streptococcus