Disease relevance of pbp2

• VraSR two-component regulatory system and its role in induction of pbp2 and vraSR expression by cell wall antimicrobials in Staphylococcus aureus [1].
• Sequencing of the vicinity of the staphylococcal pbp2 gene and transcriptional analysis by primer extension and promoter fusions were used to show that pbp2 is part of an operon that also includes a gene with high homology to prfA of Bacillus subtilis [2].
• The selected 29ca showed anti-MRSA activity comparable to that of vancomycin (VCM) both in vitro and in vivo, high affinity (IC50)=2.7 microg/ml) for penicillin binding protein 2' (PBP2') of MRSA and potent activity against Gram-negative bacteria as well [3].

High impact information on pbp2

• However, when a disk diffusion assay that can detect induction of genes over an extended time period was used, induction of the pbp2 operon was mediated by some beta-lactams, including oxacillin; this induction was independent of vraS [1].
• Transcriptional induction of the penicillin-binding protein 2 gene in Staphylococcus aureus by cell wall-active antibiotics oxacillin and vancomycin [4].
• Its activity is due to a high affinity of the penicillin-binding protein 2' in MRSA, an affinity which was approximately 1,050 times as high as that for flomoxef [5].
• Increased production of penicillin-binding protein 2, increased detection of other penicillin-binding proteins, and decreased coagulase activity associated with glycopeptide resistance in Staphylococcus aureus [6].
• The PBP 2 gene (pbpB) was cloned from an expression library of a methicillin-susceptible strain of S. aureus (209P), and its entire sequence was compared with that of the pbpB gene from strains BB255, BB255R, and CDC6 [7].

Chemical compound and disease context of pbp2

• Increased susceptibility to cephamycin-type antibiotics of methicillin-resistant Staphylococcus aureus defective in penicillin-binding protein 2 [8].
• In a study of clinical isolates previously characterized as either MRSA or methicillin-susceptible Staphylococcus aureus (MSSA) by antibiotic susceptibility testing, 231 specimens of 232 MRSA were PBP2' positive by latex agglutination, and the 87 specimens of MSSA were all negative [9].
• Fosfomycin enhances the expression of penicillin-binding protein 2 in methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains [10].

Biological context of pbp2

• Although pbp2 transcription decreased in the vraS mutants, overexpression of the pbp2 operon did not restore resistance [11].
• Furthermore, the nucleotide sequences of sgtA, sgtB and pbp2 in the mutant were identical to those of the parent [12].
• We now show that introduction of the intact pbp2 gene with its two newly identified promoters into the chromosome of the transposon mutant resulted in the full recovery of high-level methicillin resistance [2].
• Point mutations in Staphylococcus aureus PBP 2 gene affect penicillin-binding kinetics and are associated with resistance [7].
• Two synthetic peptides 31 and 32 amino acids in length were prepared as deduced from a known amino acid sequence of penicillin-binding protein 2' (PBP2') of methicillin-resistant Staphylococcus aureus [13].

Anatomical context of pbp2

• The VraS/VraR two-component regulatory system is inducible by cell-wall antimicrobials (beta-lactams, glycopeptides) and controls transcriptional induction of many cell-wall genes including pbp2 and itself [11].

Associations of pbp2 with chemical compounds

• These data demonstrate that although expressions of mecA and pbp2 are required for oxacillin resistance, they are not sufficient [11].
• It was recently reported that transposon inactivation of pbp2 causes a reduction in methicillin resistance, but complementation experiments were not fully successful [2].
• With high-resistance strains, flomoxef induced PBP 2' to an extent similar to that of cefazolin in both penicillinase-producing and -negative strains, except for one strain in which the induction did not occur [14].
• Penicillin-binding protein 2', 2, and 4 fractions were scarcely detectable in MR S. aureus strains grown in the presence of fosfomycin at concentrations of 0.25 MIC and 0.5 MIC, respectively [15].
• With penicillinase-producing strains of the low-resistance group, cefazolin, cefamandole, and cefmetazole induced PBP 2' production about 5-fold, while flomoxef induced production 2.4-fold or less [14].

Analytical, diagnostic and therapeutic context of pbp2

• Western blot (immunoblot) analysis demonstrated specific binding of the antibodies to PBP2' of a methicillin-resistant S. aureus strain [13].
• An immunoradiometric assay was developed by using these antibodies for simple detection of PBP2' [13].
• Experimental proof that this point mutation was responsible for the drug-resistant phenotype, and also for the decreased PBP2 affinity and reduced cell wall cross-linking, was provided by allelic replacement experiments and site-directed mutagenesis [16].
• One specimen identified as MRSA by susceptibility testing but PBP2' negative by latex agglutination was confirmed as mecA gene negative by PCR [9].
• The difference in the RT-PCR results among the polyoxometalates suggests that there remain other factors for the inhibition of PBP2' production such as post-transcription process [17].

References