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Biochemical Characterization of Streptococcus pneumoniae Penicillin-Binding Protein 2b and Its Implication in β-Lactam Resistance
- Source :
- Antimicrobial Agents and Chemotherapy. 48:1848-1855
- Publication Year :
- 2004
- Publisher :
- American Society for Microbiology, 2004.
-
Abstract
- Extensive use of β-lactam antibiotics has led to the selection of pathogenic streptococci resistant to β-lactams due to modifications of the penicillin-binding proteins (PBPs). PBP2b from Streptococcus pneumoniae is a monofunctional (class B) high-molecular-weight PBP catalyzing the transpeptidation between adjacent stem peptides of peptidoglycan. The transpeptidase domain of PBP2b isolated from seven clinical resistant (CR) strains contains 7 to 44 amino acid changes over the sequence of PBP2b from the R6 β-lactam-sensitive strain. We show that the extracellular soluble domains of recombinant PBP2b proteins (PBP2b*) originating from these CR strains have an in vitro affinity for penicillin G that is reduced by up to 99% from that of the R6 strain. The Thr446Ala mutation is always observed in CR strains and is close to the key conserved motif (S 443 SN). The Thr446Ala mutation in R6 PBP2b* displays a 60% reduction in penicillin G affinity in vitro compared to that for the wild-type protein. A recombinant R6 strain expressing the R6 PBP2b Thr446Ala mutation is twofold less sensitive to piperacillin than the parental S. pneumoniae strain. Analysis of the Thr446Ala mutation in the context of the PBP2b CR sequences revealed that its influence depends upon the presence of other unidentified mutations.
- Subjects :
- DNA, Bacterial
Penicillin binding proteins
Molecular Sequence Data
Penicillins
Muramoylpentapeptide Carboxypeptidase
Biology
medicine.disease_cause
Pneumococcal Infections
beta-Lactam Resistance
law.invention
Microbiology
chemistry.chemical_compound
Bacterial Proteins
Mechanisms of Resistance
law
Streptococcus pneumoniae
polycyclic compounds
medicine
Humans
Penicillin-Binding Proteins
Pharmacology (medical)
Amino Acid Sequence
Cloning, Molecular
Serotyping
Peptide sequence
Pharmacology
Mutation
Strain (chemistry)
Penicillin G
Aminoacyltransferases
Penicillin
Infectious Diseases
Hexosyltransferases
chemistry
Peptidyl Transferases
Recombinant DNA
Peptidoglycan
Carrier Proteins
medicine.drug
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....1f0297550aec8a37c649b0a9c27d6ed8