title: Insight into the Diversity of Penicillin-Binding Protein 2x Alleles and Mutations in Viridans Streptococci.
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 ofStreptococcus pseudopneumoniaeas a new species, which was distinguished from closely related pathogenicS. pneumoniaeand commensalS. mitisby a variety of physiological and molecular biological tests. Forty-one atypicalS. pneumoniaeisolates have been collected at the German National Reference Center for Streptococci (GNRCS). Multilocus sequence typing (MLST) confirmed 35 isolates as the speciesS. pseudopneumoniaeA comparison with thepbp2xsequences from 120 commensal streptococci isolated from different continents revealed thatpbp2xis distinct among penicillin-susceptibleS. pseudopneumoniaeisolates. Four penicillin-binding protein x (PBPx) alleles of penicillin-sensitiveS. mitisaccount for most of the diverse sequence blocks in resistantS. pseudopneumoniae,S. pneumoniae, andS. mitis, andS. infantisandS. oralissequences were found inS. pneumoniaefrom Japan. PBP2x genes of the family of mosaic genes related topbp2xin theS. pneumoniaeclone Spain23F-1 were observed inS. oralisandS. infantisas 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.
authors.affiliation: German National Reference Center for Streptococci, Department of Medical Microbiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: van der Linden
authors.affiliation: German National Reference Center for Streptococci, Department of Medical Microbiology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Otten
authors.affiliation: Department of Microbiology, University of Kaiserslautern, Kaiserslautern, Germany.|Novo Nordisk Pharma GmbH, Mainz, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Bergmann
authors.affiliation: Department of Microbiology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Latorre
authors.affiliation: Microbiology Department, Hospital Universitario de Bellvitge-IDIBELL, Ciber de Enfermedades Respiratorias, University of Barcelona, Barcelona, Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Liñares
authors.affiliation: Department of Microbiology, University of Kaiserslautern, Kaiserslautern, Germany hakenb@rhrk.uni-kl.de.
authors.forename: Regine
authors.initials: R
authors.lastname: Hakenbeck
mesh_terms: D000483:Alleles; D020134:Catalytic Domain / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D009154:Mutation / Q000235:genetics; D010403:Penicillin Resistance / Q000235:genetics*; D046915:Penicillin-Binding Proteins / Q000235:genetics*; D013290:Streptococcal Infections / Q000188:drug therapy / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000302:isolation & purification; D034363:Viridans Streptococci / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D004269:DNA, Bacterial; D046915:Penicillin-Binding Proteins; C072223:PBP 2x protein, Streptococcus
keywords: PBP2x; PBP2x mutation; S. pseudopneumoniae; penicillin resistance; viridans streptococci