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1994 Fiscal Year Final Research Report Summary

Analysis of regulatory mechanism of expression of drug-resistance genes and their evolution

Research Project

Project/Area Number 04454535
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 生物系薬学
Research InstitutionMEIJI COLLEGE OF PHARMACY

Principal Investigator

OGAWARA Hiroshi  Meiji College of Pharmacy, 薬学部, 教授 (00097198)

Co-Investigator(Kenkyū-buntansha) HIGASHI Kyoichiro  Assistant Professor, 薬学部, 助手 (10189748)
URABE Hiroaki  Assistant Professor, 薬学部, 助手 (20201361)
Project Period (FY) 1992 – 1994
Keywordsdrug resistance / gene expression / beta-lactamase / penicillin-binding protein / nucleotide sequence / evolution / pseudogene
Research Abstract

(1) Analysis of activator-regulator genes for beta-lactamase in Streptomyces cacaoi.
There were two activator-regulator genes in the upstream of the structural gene of the beta-lactamase. Transcription for the activator genes commenced at the translational initiation codon or within a few nucleotides from the translational start site. These genes are also necessary for the induction.
(2) Sequence analysis of three type II beta-lactamases from Streptomyces.
The deduced amino acid sequences of beta-lactamases from S.cellulosae KCCS0127, S.lavendulae KCCS0263 and S.fradiae Y59 were very close to those of class A beta-lactamases but completely different from class D beta-lactamases. This is contrary to the expectation from their substrate specificity and their property of binding blue dextran and NADP^+.
(3) Analysis of amino acid sequences involved in the binding to blue-dextran.
To determine which amino acid residues are critical in binding activity to blue dextran, chimera beta-lactamases we … More re constructed and their binding abilities were determined. Blue dextran binding may depend more on overall conformation of about two-thirds of the beta-lactamase molecule from the N-terminus than on the primary structure.
(4) Analysis of sequence similarity of beta-lactamases and their phylogenetic tree.
A phylogenetic tree constructed on the basis of the amino acid sequences of 47 beta-lactamases and the computeraided analysis suggests that beta-lactamases can be classified into six groups. The tree provides more detailed classification and time-scale mutual relationships and predicts new types of p-lactamases that may be found. In addition, the class A beta-lactamases are clearly divided into three groups and some eukaryotic proteins have a low but significant evolutionary relatedness.
(5) Gene transfer of a part of beta-lactamase gene?
The amino acid sequence deduced from the nucleotide sequence of the upstream region of cytochrome c oxidase subunit II from Paracoccus denitrificans had an unusually high score of homology to that of a portion of beta-lactamases from Gram-negative bacteria. It is suggested that the nucleotide sequence was positioned by a transfer of a part of a beta-lactamase gene formed as a result of gene duplication or it was formed by a deletion of the essential region of the beta-lactamase gene.
(6) Similarity analysis of beta-lactam-interacting proteins and the phylogenetic tree.
Fifty tree beta-lactam-interacting proteins were classidied to six groups. Three DD-peptidases from Streptomycetes were distinguished into three different groups. Together with the fact that apparently unrelated proteins like Pseudomonas esterase and O.anthropi D-aminopeptidase show high scores of similarity, it is speculated that these beta-lactam-interacting proteins including beta-lactamases now are formed as a result of very rapid divergent evolution, and the esterase and D-aminopeptidase activities in these proteins may be acquired as a result of such rapid evolution. Less

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] H.Urabe: "Nucleotide sequence and tianscriptional analysis of activotor-regulator proteins for β-lactamase in Streptomyces cacaoi." J.Bacterisl.174. 2834-2842 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Ogawara: "Nucleotide sequence of a gene encoding β-lactamase from Streptomyces cellulosae" Gene. 124. 111-114 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Ogawara: "Phylogenetic tree and sequence similarity of β-lactamases." Mol.Phylogenetics Evolution. 2. 97-111 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Ogawara: "Gene transfer of a part of a β-lactamase gene?" Microbiol,Imswnol.37. 399-403 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Karai: "Cloning,sequencing and site-directed mutagenesis of β-lactamase gene from Streptomyces fradiae Y59." Autiwicrob.Ageuts Chemother.39. 260-263 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Urabe: "Cloning,sequencing and expression of seriue/threonine Kinase genes from Streptomyces coelicolor A3(2)" Gene. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小河原 宏(編): "遺伝子組換え(第2版)" 広川書店, 281 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小河原 宏(共著): "バイオサイエンスと放線菌(堀田国之,堀之内末治編)" 医学出版センター, 283 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Urabe, H.Ogawara: "Nucleotide sequence and transcriptional analysis of activator-regulator proteins for beta-lactamase in Streptomyces cacaoi." J.Bacteriol.174 (9). 2834-2842 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ogawara: "Nucleotide sequence of a gene encoding beta-lactamase from Streptomyces cellulosae." Gene. 124 (1). 111-114 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ogawara, H.Kasama, K.Nashimoto, M.Ohtsubo, K.Higashi, H.Urabe: "Cloning, nucleotide sequence and expression of argG from Streptomyces lavendulae." Gene. 125. 91-96 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ogawara, K.Kuma, T.Miyata: "Gene transfer of a part of a beta-lactamase gene? Microbiol." Immunology. 37 (5). 399-403 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ogawara: "Phylogenetic tree and sequence similarity of beta-lactamases." Mol.Phylogenetics Evolution. 2 (2). 97-111 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Sendouda, H.Urabe, H.Ogawara: "Cloning, nucleotide sequence and expression of beta-lactamase gene from Streptomyces lavendulae." FEMS Microbiol.Lett.112 (3). 343-348 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Urabe, H.Ogawara: "Involvement of two genes in the induction of beta-lactamase in Streptomyces cacaoi." Actinomycetologica. 7 (2). 65-67 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Kurai, H.Urabe, H.Ogawara: "Cloning, sequencing and site-directed mutagenesis of beta-lactamase gene from Streptomyces fradiae Y59. Antimicrob." Agents Chemother.39 (1). 260-263 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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