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Gene Review

pbp2b  -  penicillin-binding protein 2B

Streptococcus pneumoniae R6

 
 
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Disease relevance of pbp2b

 

High impact information on pbp2b

  • All six penicillin-binding protein (PBP) genes, namely, pbp1a, pbp1b, pbp2a, pbp2b, pbp2x, and pbp3, of 40 Streptococcus pneumoniae clinical isolates, including penicillin-resistant S. pneumoniae isolates collected in Japan, were completely sequenced [5].
  • This determinant (from the French isolate) was, however, able to transform an R6 mutant harboring pbp2x, pbp2b, and pbp1a genes from a Hungarian clone with an extremely high level of penicillin resistance so that it had increased levels of penicillin resistance [6].
  • DNA sequence analysis of the pbp2x, pbp2b, and pbp1a genes revealed extensive sequence divergence in all six isolates compared to the sequences of the genes of penicillin-susceptible strain R6 [6].
  • Sequence analysis results of the pbp2b and pbpX alleles from these strains were in keeping with acquired penicillin resistance [7].
  • 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 [8].
 

Biological context of pbp2b

  • These results suggest that amino acid substitution of Thr-371 contributes to the development of penicillin resistance in PRSP strains with altered pbp2x and pbp2b genes [8].
  • As both strains expressed the serotype 23F capsule, were very closely related in overall genotype, and possessed identical or closely related mosaic pbp1a, pbp2x, and pbp2b genes, it is likely that they have arisen from a recent common ancestor [9].
  • An analysis of the nucleotide sequences of the pbp2b genes from seven strains revealed an unique direct repeat of 9 nucleotides (TGGTATACT) between active-site serine (residue 385) and Ser-X-Asn (residues 442 to 444) motifs [10].
  • This study assessed the relationship between acquired resistance and virulence in single- and double-isogenic penicillin-resistant (Peni-R) mutants obtained by transformation of a virulent penicillin-susceptible recipient strain with pbp2b and pbpX polymerase chain reaction fragments from a Peni-R donor strain [7].
  • The pbp2b genes of most Korean isolates showed novel mosaic mutations due to horizontal gene transfer [11].
 

Anatomical context of pbp2b

  • High prevalence of Streptococcus pneumoniae with mutations in pbp1a, pbp2x, and pbp2b genes of penicillin-binding proteins in the nasopharynx in children in Japan [3].
  • Penicillin binding protein 2b was also detected in rat middle ear mucosa recovered 5 weeks after middle ear challenge with S. pneumoniae [12].
  • Compared to other methods, mechanical homogenization in TRIZOL was the most efficient for releasing microbial RNA, and addition of polyinosinic acid (Poly I) as an RNA carrier increased the assay sensitivity to 10(2) colony forming units when detected by RT-PCR amplification of 16S ribosomal RNA or messenger RNA for penicillin binding protein 2b [12].
 

Associations of pbp2b with chemical compounds

  • Those conferring maximal resistance to either cefotaxime (pbp2x) or piperacillin (pbp2b) were obtained after transformation of the susceptible laboratory strain R6 with the PCR-amplified PBP genes and selection on agar with various concentrations of the antibiotic [13].
  • 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 [8].
  • The multivariate analysis showed statistically significant correlation between higher MIC of penicillin and cephem and pbp1a mutation while no significant contribution of pbp2x and pbp2b to the resistance was demonstrated [14].
 

Other interactions of pbp2b

  • Restriction fragment patterns of pbp2b, pbp2x, and pspA were conserved within the majority of isolates that shared macrorestriction types [15].
  • These results also indicate that it may be possible to identify PSSP and penicillin-resistant S. pneumoniae by applying PCR using a combination of primers to detect the susceptible pbp2b gene, resistant pbp2b gene mutations, and the lytA gene [16].
 

Analytical, diagnostic and therapeutic context of pbp2b

  • Isolates were characterized by pulsed-field gel electrophoresis; multilocus sequence typing; determination of pbp1a, pbp2b, and pbp2x gene restriction patterns; and partial sequencing of these pbp genes [17].
  • Restriction enzyme analyses of the pbp1a, pbp2b, and pbp2x genes revealed 12, 12, and 19 different patterns, respectively; and a total of 43 different PBPs types were demonstrated [18].

References

  1. Activities of ceftobiprole and other beta-lactams against Streptococcus pneumoniae clinical isolates from the United States with defined substitutions in penicillin-binding proteins PBP 1a, PBP 2b, and PBP 2x. Davies, T.A., Shang, W., Bush, K. Antimicrob. Agents Chemother. (2006) [Pubmed]
  2. Molecular epidemiology survey of penicillin-susceptible and -resistant Streptococcus pneumoniae recovered from patients with meningitis in France. Doit, C., Picard, B., Loukil, C., Geslin, P., Bingen, E. J. Infect. Dis. (2000) [Pubmed]
  3. High prevalence of Streptococcus pneumoniae with mutations in pbp1a, pbp2x, and pbp2b genes of penicillin-binding proteins in the nasopharynx in children in Japan. Hotomi, M., Billal, D.S., Shimada, J., Suzumoto, M., Yamauchi, K., Fujihara, K., Yamanaka, N. ORL J. Otorhinolaryngol. Relat. Spec. (2006) [Pubmed]
  4. Alterations of pbp1a, pbp2b, and pbp2x in Streptococcus pneumoniae isolates from children with otolaryngological infectious disease in the Sapporo district of Japan. Harimaya, A., Yokota, S., Sato, K., Koizumi, J., Yamazaki, N., Himi, T., Fujii, N. J. Infect. Chemother. (2006) [Pubmed]
  5. Complete sequences of six penicillin-binding protein genes from 40 Streptococcus pneumoniae clinical isolates collected in Japan. Sanbongi, Y., Ida, T., Ishikawa, M., Osaki, Y., Kataoka, H., Suzuki, T., Kondo, K., Ohsawa, F., Yonezawa, M. Antimicrob. Agents Chemother. (2004) [Pubmed]
  6. Analysis of penicillin-binding protein genes of clinical isolates of Streptococcus pneumoniae with reduced susceptibility to amoxicillin. du Plessis, M., Bingen, E., Klugman, K.P. Antimicrob. Agents Chemother. (2002) [Pubmed]
  7. Complex relationship between acquisition of beta-lactam resistance and loss of virulence in Streptococcus pneumoniae. Rieux, V., Carbon, C., Azoulay-Dupuis, E. J. Infect. Dis. (2001) [Pubmed]
  8. Association of a thr-371 substitution in a conserved amino acid motif of penicillin-binding protein 1A with penicillin resistance of Streptococcus pneumoniae. Asahi, Y., Ubukata, K. Antimicrob. Agents Chemother. (1998) [Pubmed]
  9. Genetic analysis of clinical isolates of Streptococcus pneumoniae with high-level resistance to expanded-spectrum cephalosporins. Coffey, T.J., Daniels, M., McDougal, L.K., Dowson, C.G., Tenover, F.C., Spratt, B.G. Antimicrob. Agents Chemother. (1995) [Pubmed]
  10. Directly repeated insertion of 9-nucleotide sequence detected in penicillin-binding protein 2B gene of penicillin-resistant Streptococcus pneumoniae. Yamane, A., Nakano, H., Asahi, Y., Ubukata, K., Konno, M. Antimicrob. Agents Chemother. (1996) [Pubmed]
  11. Unique variations of pbp2b sequences in penicillin-nonsusceptible Streptococcus pneumoniae isolates from Korea. Baek, J.Y., Ko, K.S., Oh, W.S., Jung, S.I., Kim, Y.S., Chang, H.H., Lee, H., Kim, S.W., Peck, K.R., Lee, N.Y., Song, J.H. J. Clin. Microbiol. (2004) [Pubmed]
  12. Evaluation of microbial RNA extractions from Streptococcus pneumoniae. Li-Korotky, H.S., Kelly, L.A., Piltcher, O., Hebda, P.A., Doyle, W.J. J. Microbiol. Methods (2007) [Pubmed]
  13. Penicillin-binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of beta-lactam antibiotics. Grebe, T., Hakenbeck, R. Antimicrob. Agents Chemother. (1996) [Pubmed]
  14. Clinical and laboratory evaluation of penicillin resistant Streptococcus pneumoniae in relation to the mutations of pbp 1a, pbp2b and pbp2x. Tanoue, S. The Kurume medical journal. (2001) [Pubmed]
  15. Genotypes of invasive pneumococcal isolates recently recovered from Italian patients. Dicuonzo, G., Gherardi, G., Gertz, R.E., D'Ambrosio, F., Goglio, A., Lorino, G., Recchia, S., Pantosti, A., Beall, B. J. Clin. Microbiol. (2002) [Pubmed]
  16. Combinational detection of autolysin and penicillin-binding protein 2B genes of Streptococcus pneumoniae by PCR. Ubukata, K., Asahi, Y., Yamane, A., Konno, M. J. Clin. Microbiol. (1996) [Pubmed]
  17. Diversity of penicillin-nonsusceptible Streptococcus pneumoniae circulating in Iceland after the introduction of penicillin-resistant clone Spain(6B)-2. Sá-Leão, R., Vilhelmsson, S.E., de Lencastre, H., Kristinsson, K.G., Tomasz, A. J. Infect. Dis. (2002) [Pubmed]
  18. Molecular Characterization of Non-Penicillin-Susceptible Streptococcus pneumoniae in Norway. Sogstad, M.K., Høiby, E.A., Caugant, D.A. J. Clin. Microbiol. (2006) [Pubmed]
 
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