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J Bacteriol. Sep 1994; 176(17): 5574–5577.
PMCID: PMC196753

Penicillin-binding protein 2b of Streptococcus pneumoniae in piperacillin-resistant laboratory mutants.

Abstract

In Streptococcus pneumoniae, alterations in penicillin-binding protein 2b (PBP 2b) that reduce the affinity for penicillin binding are observed during development of beta-lactam resistance. The development of resistance was now studied in three independently obtained piperacillin-resistant laboratory mutants isolated after several selection steps on increasing concentrations of the antibiotic. The mutants differed from the clinical isolates in major aspects: first-level resistance could not be correlated with alterations in the known PBP genes, and the first PBP altered was PBP 2b. The point mutations occurring in the PBP 2b genes were characterized. Each mutant contained one single point mutation in the PBP 2b gene. In one mutant, this resulted in a mutation of Gly-617 to Ala within one of the homology boxes common to all PBPs, and in the other two cases, the same Gly-to-Asp substitution at the end of the penicillin-binding domain had occurred. The sites affected were homologous to those determined previously in the S. pneumoniae PBP 2x of mutants resistant to cefotaxime, indicating that, in both PBPs, similar sites are important for interaction with the respective beta-lactams.

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  • Adam M, Damblon C, Jamin M, Zorzi W, Dusart V, Galleni M, el Kharroubi A, Piras G, Spratt BG, Keck W, et al. Acyltransferase activities of the high-molecular-mass essential penicillin-binding proteins. Biochem J. 1991 Oct 15;279(Pt 2):601–604. [PMC free article] [PubMed]
  • Brannigan JA, Tirodimos IA, Zhang QY, Dowson CG, Spratt BG. Insertion of an extra amino acid is the main cause of the low affinity of penicillin-binding protein 2 in penicillin-resistant strains of Neisseria gonorrhoeae. Mol Microbiol. 1990 Jun;4(6):913–919. [PubMed]
  • Dowson CG, Coffey TJ, Kell C, Whiley RA. Evolution of penicillin resistance in Streptococcus pneumoniae; the role of Streptococcus mitis in the formation of a low affinity PBP2B in S. pneumoniae. Mol Microbiol. 1993 Aug;9(3):635–643. [PubMed]
  • Dowson CG, Hutchison A, Spratt BG. Extensive re-modelling of the transpeptidase domain of penicillin-binding protein 2B of a penicillin-resistant South African isolate of Streptococcus pneumoniae. Mol Microbiol. 1989 Jan;3(1):95–102. [PubMed]
  • Dowson CG, Hutchison A, Spratt BG. Nucleotide sequence of the penicillin-binding protein 2B gene of Streptococcus pneumoniae strain R6. Nucleic Acids Res. 1989 Sep 25;17(18):7518–7518. [PMC free article] [PubMed]
  • Ghuysen JM. Serine beta-lactamases and penicillin-binding proteins. Annu Rev Microbiol. 1991;45:37–67. [PubMed]
  • Hakenbeck R, Briese T, Ellerbrok H. Antibodies against the benzylpenicilloyl moiety as a probe for penicillin-binding proteins. Eur J Biochem. 1986 May 15;157(1):101–106. [PubMed]
  • Hakenbeck R, Tornette S, Adkinson NF. Interaction of non-lytic beta-lactams with penicillin-binding proteins in Streptococcus pneumoniae. J Gen Microbiol. 1987 Mar;133(3):755–760. [PubMed]
  • Hedge PJ, Spratt BG. Resistance to beta-lactam antibiotics by re-modelling the active site of an E. coli penicillin-binding protein. Nature. 1985 Dec 5;318(6045):478–480. [PubMed]
  • Hedge PJ, Spratt BG. Amino acid substitutions that reduce the affinity of penicillin-binding protein 3 of Escherichia coli for cephalexin. Eur J Biochem. 1985 Aug 15;151(1):111–121. [PubMed]
  • Laible G, Hakenbeck R. Penicillin-binding proteins in beta-lactam-resistant laboratory mutants of Streptococcus pneumoniae. Mol Microbiol. 1987 Nov;1(3):355–363. [PubMed]
  • Laible G, Hakenbeck R, Sicard MA, Joris B, Ghuysen JM. Nucleotide sequences of the pbpX genes encoding the penicillin-binding proteins 2x from Streptococcus pneumoniae R6 and a cefotaxime-resistant mutant, C506. Mol Microbiol. 1989 Oct;3(10):1337–1348. [PubMed]
  • Laible G, Spratt BG, Hakenbeck R. Interspecies recombinational events during the evolution of altered PBP 2x genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Mol Microbiol. 1991 Aug;5(8):1993–2002. [PubMed]
  • Martin C, Briese T, Hakenbeck R. Nucleotide sequences of genes encoding penicillin-binding proteins from Streptococcus pneumoniae and Streptococcus oralis with high homology to Escherichia coli penicillin-binding proteins 1a and 1b. J Bacteriol. 1992 Jul;174(13):4517–4523. [PMC free article] [PubMed]
  • Martin C, Sibold C, Hakenbeck R. Relatedness of penicillin-binding protein 1a genes from different clones of penicillin-resistant Streptococcus pneumoniae isolated in South Africa and Spain. EMBO J. 1992 Nov;11(11):3831–3836. [PMC free article] [PubMed]
  • Muñoz R, Dowson CG, Daniels M, Coffey TJ, Martin C, Hakenbeck R, Spratt BG. Genetics of resistance to third-generation cephalosporins in clinical isolates of Streptococcus pneumoniae. Mol Microbiol. 1992 Sep;6(17):2461–2465. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]

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