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Association of Additional Amino Acid Substitutions in pbp2X and pbp2b Genes in High-Level b-lactam Resistance of Streptococcus pneumoniae.

SHIBASAKI Y, CHIBA N, HASEGAWA K, APPELBAUM P, NAGAI K, UBUKATA K; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 76.

Pharmaceutical Res. Ctr., Meiji Seika Kaisha, Ltd., Yokohama, Japan

BACKGROUND: We previously reported that alterations of pbp1a, -2x, and -2b genes affected the MIC level of b-lactams in penicillin (Pc)-resistant Streptcoccus pneumoniae (PRSP). Recently, highly b-lactam-resistant PRSP ( MIC: >/= 4 microg/ml for Pc, >/= 8 microg/ml for ampicillin (Amc), and >/= 4 microg/ml for Cefotaxime (Ctx)) have been found in Japan. It was suggested that the high resistance of these strains is caused by further alterations of pbp genes in addition to that detected in common PRSP. In this study, we clarify the influence of additional alterations on MIC values of b-lactams in high-level resistant PRSP.METHODS: Nucleotide sequences of transpeptidase regions of pbp1a, -2x, and -2b genes in PRSP from Japan, USA, Greece, Slovakia, and Rumania were determined and the substitutions of amino acids were compared with the results reported previously.RESULTS: Group I strains of PRSP were frequently isolated in Japan. In these strains, 371Thr was substituted to Ala in PBP1A, as well as 338Thr[TM] Ala in PBP2X, and 446Thr[TM] Ala in PBP2B. These substitutions were detected in or adjacent to conserved amino acid motifs. In addition to such substitutions, 339Met[TM] Phe in PBP2X occurred in group II strains showing high MIC for Ctx. In group III strains, which high MIC for Amc, 10 amino acid substitutions were observed around the KTG motif in PBP2B. Group IV strains showed high resistance to all b-lactams tested, and had the substitutions found in both Groups II and III [table: see text]. Conclusion: These results suggested that additional amino acids substitutions caused by alterations of pbp genes developed further resistance of b-lactams.KEYWORDS: PBP; Penicillin resistance; Streptococcus pneumoniae

Publication Types:
  • Meeting Abstracts
Keywords:
  • Amino Acid Substitution
  • Antigens, Bacterial
  • Base Sequence
  • Greece
  • Japan
  • Lactams
  • Microbial Sensitivity Tests
  • Penicillin Resistance
  • Penicillins
  • Peptidyl Transferases
  • Romania
  • Slovakia
  • Streptococcus pneumoniae
  • genetics
  • immunology
Other ID:
  • GWAIDS0010914
UI: 102248412

From Meeting Abstracts




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