Disease relevance of pbpA

• We determined the nucleotide sequence between 1,903 and 3,097 bp of pbp1a, which encodes the transpeptidase domain of PBP 1A, from clinical isolates of penicillin-resistant Streptococcus pneumoniae (PRSP) serotypes 19 (n = 8), 6 (n = 9), 23 (n = 6), and 14 (n = 2) and two penicillin-susceptible S. pneumoniae (PSSP) isolates [1].
• In Proteus vulgaris, binding was highest to PBP4, followed by PBP1A, PBP2 and PBP3 [2].
• In E. coli, faropenem showed the highest affinity for PBP2, followed by PBP1A, PBP1B, PBP3 and PBP4 [2].

High impact information on pbpA

• To explain these data, we favour the interpretation that horizontal gene transfer in natural populations has distributed genes encoding altered forms of PBP1A, -2B and -2X to distinct evolutionary lineages of S. pneumoniae [3].
• However, PBP 1A mutants presented shorter glycan chains (by 30%) and a relative decrease (25%) in one monomer stem peptide [4].
• Our mutagenesis study has investigated all amino acid mutations in the penicillin-binding domain of PBP 1A from Hungarian pneumococcal isolate 3191 to determine the importance of every mutation in the development of penicillin and cefotaxime resistance [5].
• In contrast, for strains (n = 4) without a substitution at Thr-371 in PBP 1A but with mutations in both pbp2x and pbp2b, penicillin MICs were 0.125 to 0.25 microgram/ml, and the affinities of their PBPs 1A were similar to that of PSSP PBPs 1A [1].
• Site-directed mutagenesis was then used to determine whether particular amino acid substitutions at specific positions in PBP 1A mediate penicillin resistance [6].

Biological context of pbpA

• We have sequenced the penicillin-binding domain of PBP 1A from penicillin-resistant South African pneumococcal isolates and have identified amino acid substitutions which are common to all the resistant isolates analyzed [6].
• Alterations in PBP 1A essential-for high-level penicillin resistance in Streptococcus pneumoniae [6].
• Pulsed-field gel electrophoresis and Southern blotting showed that the capsular genes specific for serotype 3 are located near the genes encoding PBP 2X and PBP 1A in the S. pneumoniae chromosome, whereas copies of the common genes (or part of them) appear to be present in different locations in the genome [7].

Associations of pbpA with chemical compounds

• For PBP 2X/2B/1A-R6 transformants, the introduction of the reversal of Thr-371 by Ser or Ala in PBP 1A decreased the MIC from 1.5 to 0.5 micrograms/ml, whereas the reversal of four consecutive amino acid substitutions (Thr-574 by Asn, Ser-575 by Thr, Gln-576 by Gly, and Phe-577 by Tyr) decreased the MIC from 1.5 to 0.375 micrograms/ml [6].
• For strains (n = 18) for which the threonine at codon 371 (Thr-371) in a conserved STMK motif of PBP 1A was substituted with an alanine or a serine (in addition to having altered pbp2x and pbp2b genes), penicillin MICs were >/= 1.0 microgram/ml [1].
• Deletion of the PBP 1A gene was therefore tolerated under laboratory conditions and appeared to have little effect on growth or susceptibility to benzylpenicillin [8].

Other interactions of pbpA

• Different protein variants of MurM (MA, MB5, MB6, MB9 and MB10), PBP1A (A-C), PBP2B (A-D) and PBP2X (A-C) were recognized, including two murM alleles not previously described [9].

Analytical, diagnostic and therapeutic context of pbpA

• Site-specific mutagenesis analysis of PBP 1A from a penicillin-cephalosporin-resistant pneumococcal isolate [5].
• Eight isolates were indistinguishable by ribotyping or multilocus enzyme electrophoresis and contained identical PBP 1A genes [10].
• Analysis using the polymerase chain reaction confirmed that the latter transformants had replaced their chromosomal copy of the PBP 1A gene with the inactivated copy of the gene [8].

References