title: All detectable high-molecular-mass penicillin-binding proteins are modified in a high-level beta-lactam-resistant clinical isolate of Streptococcus mitis.
abstract: All detectable high-molecular-mass penicillin-binding proteins (HMM PBPs) are altered in a clinical isolate of Streptococcus mitis for which the beta-lactam MICs are increased from those previously reported in our region (cefotaxime MIC, 64 microg/ml). These proteins were hardly detected at concentrations that saturate all PBPs in clinical isolates and showed, after densitometric analysis, 50-fold-lower radiotracer binding. Resistance was related to mosaic structure in all HMM PBP-coding genes, where critical region replacement was complemented not only by substitutions already reported for the closely related Streptococcus pneumoniae but also by other specific replacements that are presumably close to the active-site serine. Mosaic structure was also presumed in a pbp1a-sensitive strain used for comparison, confirming that these structures do not unambiguously imply, by themselves, detectable critical changes in the kinetic properties of these proteins.
authors.affiliation: Laboratorio de resistencia microbiana, Cátedra de Microbiología. Departamento de Microbiología, Inmunología y Biotecnología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Amoroso
authors.forename: D
authors.initials: D
authors.lastname: Demares
authors.forename: M
authors.initials: M
authors.lastname: Mollerach
authors.forename: G
authors.initials: G
authors.lastname: Gutkind
authors.forename: J
authors.initials: J
authors.lastname: Coyette
mesh_terms: D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000032:analysis; D005784:Gene Amplification; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000235:genetics / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D013291:Streptococcus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D018440:beta-Lactam Resistance / Q000502:physiology*; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D012336:RNA, Ribosomal, 16S; D047090:beta-Lactams; C072223:PBP 2x protein, Streptococcus; C095500:SodA protein, Bacteria; D013482:Superoxide Dismutase; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase