Role of shignal transduction of muropeptide by overexposing AmpC enzyme arises

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14370096
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kitasato University
• Principal Investigator: INOUE Matsuhisa Kitasato Univ., School of Medicine, Professor, 医学部, 教授 (10008336)
• Co-Investigator(Kenkyū-buntansha): OKAMOTO Ryouichi Kitasato Univ., School of Medicine, Assistant Professor, 医学部, 講師 (30224083) ; KITASATO Hidero Kitasato Univ., Allied Health Science, Professor, 医療衛生学部, 教授 (90195256)
• Project Period (FY): 2002 – 2004
• Keywords: gram-negative bacteria / class C β-lactamase / regulation of β-lactamase / cephem resistance / permense / amidase / fragment of pepuchidoglyea / muropeptide

Research Abstract

Chromosomally encoded versions of AmpC β-lactamases are particularly importance in clinical isolates of gram-negative bacteria. The molecules that serves as both repressor and the activator of ampC transcription is AmpR. Under without β-lactams, AmpR is present as a repressor by virture of its interaction with a muropeptide. In the setting of high concentrations of cell-wall breakdown product muropeptides, however, muropeptide is displaces AmpR to an activator of ampC transcription. The ease of selection of the AmpR mutations at a frequency of about 10^<-6> strongly suggests that AmpD or AmpR mutants could frequently emerge in the clinical setting. 21 cephem resistant Enterobacter cloacae exhibited AmpC overproduction due to either AmpD or AmpR mutation. E.coli plasmid pKu601 was characterized as having a novel plasmid encoded AmpC enzyme, CFE-1, with an mutation in the ampR gene, in which the Asp at position 135 is changed to Ala. The one point mutant for ampG gene was isolated by examining E.cloacae that expressed low levels of β-lactam constitutively. A single knockout for PBP2 or PBP3 E.cloacae mutants, the data revealed only about a two-fold reduction in AmpC activity to compare with that of wild typw strain.

Research Products

• [Journal Article] Characterization of ermB gene transposition by Tn1545 and Tn917 in macrolide-resistant Streptococcus pneumoniae isolates., 2005 (2005)
  • Author(s): Okits, N., H.Yano, R.Nakano, Y.Hosaka, R.Okamoto, T.Kobayashi, M.Inoue
  • Journal Title: J Clin Microbiol 43 Pages: 168-173
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Gene mutations responsible for overproduction of AmpC β-lactamase in some Enterobacter cloacae clinical isolates. (2005)
  • Author(s): Kaneko, K., Y.Sato, Y.Murakami, H.Takimoto, Y.Kumazawa, M.Inoue
  • Journal Title: J.Clin Microbiol 43(6):,2005 43 Pages: 2955-2958
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] PROTEKT 1999-2000 : a multicentre study of the antimicrobial susceptibility of respiratory tract pathogens in Japan. (2005)
  • Author(s): Inoue, M., Kohno, S., Kaku, M., Yamaguchi, K., Igari, J., Yamanaka, K.
  • Journal Title: Int J Infect Dis 9 Pages: 27-36
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of ermB gene transposition by Tn1545 and Tn917 in macrolide-resistant Streptococcus pneumoniae isolates. (2005)
  • Author(s): Okitsu Naohiro, Kaieda, S., Yano, H., Nakano, R., Hosaka, Y., Okamoto, R., Kobayashi, T., Inoue, M.
  • Journal Title: J Clin Microbiol 43 Pages: 168-173
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Use of the restriction enzyme EcoR1 for pulse-field gel electrophoretic analysis of Helicobacter pylori. (2005)
  • Author(s): Hosaka, Y., Irinoda, K., Nakano, R., Tanabe, S., Koizumi, W., Saigenji, K., Inoue, M.
  • Journal Title: J Clin Microbiol 43 Pages: 931-932
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Gene mutations responsible foroverproduction of AmpC β-lactamase in some Enterobacter cloacae clinical isolates. (2005)
  • Author(s): Kaneko, K., Okamoto, R., Nakano, R., Kawakami, S., Inoue, M.
  • Journal Title: J.Clin Microbiol 43(6) Pages: 2955-2958
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] An epidemiological study of the susceptibility and frequency of multiple-drug-resistant strains of Pseudomonas aeruginosa isolated at medical institutes nationwide in Japan (2005)
  • Author(s): Tuji, A., Kobayashi, I., Oguri, T., Inoue, M., Yabuuchi, E., Goto, S.
  • Journal Title: J Infect Chemother 11 Pages: 64-70
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Isertion sequence ISEcpl increases expression of the plasmid-encoded AmpC β-lactamase CMY-4 originated from Citrobacter freundii (2005)
  • Author(s): Nakano, R., Okamoto, R., Inoue, M.
  • Journal Title: Antimicrob Agents Chemother (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Bacterial β-lactam resistance enhances host inflammatory response via innate immunity. (2005)
  • Author(s): Kaneko, K., Sato, Y., Murakami, Y., Takimoto, H., Kumazawa, Y., Inoue, M.
  • Journal Title: Antimicrobial Agents Chemother (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] AmpC β-lactamaseindu-ction is derived from ampC in Enterobacter cloacae. (2005)
  • Author(s): Nakano, Yumiko, Nakano, R., Kaneko, K., Okamoto, R., Inoue, M.
  • Journal Title: Antimicrob Agents Chemother (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] PROTEKT 1999-2000 : a multicentre study of the antibiotic susceptibility of respiratory tract pathogens in Hong Kong, Japan and South Korea (2004)
  • Author(s): Inoue, M., N.Y.Lee, S.W.Hong, K.Lee, D.Felmingham
  • Journal Title: Int J Antimicrobial Agents 23 Pages: 44-51
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] CFE-1, anovelplasmid-encoded AmpC β-lactamase with an ampR gene originating from Citrobacter freundii. 2004 (2004)
  • Author(s): Nakano, R., R.Okamoto, Y.Nakano, K.Kaneko, N.Okitsu, Y.Hosaka, M.Inoue
  • Journal Title: Antimicrob Agents Chemother. 48 Pages: 1151-1158
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] PROTEKT 1999-2000 : a multicentre study of the antibiotic susceptibility of respiratory tract pathogens in Hong Kong, Japan and South Korea (2004)
  • Author(s): Inoue, M., Lee, N.Y., Hong, S.W., Lee, K., Felmingham, D
  • Journal Title: Int J Antimicrobial Agents 23 Pages: 44-51
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] CFE-1, anovelplasmid-encoded AmpC β-lactamase with an ampR gene originating from Citrobacter freundii. (2004)
  • Author(s): Nakano, R., Okamoto, R., Nakano, Y., Kaneko, K., Okitsu, N., Hosaka, Y., Inoue, M.
  • Journal Title: Antimicrob Agents Cemother 8 Pages: 1151-1158
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A Klebsiella pneumoniae producing three kinds of class A β-Lactamases encoded by one single plasmid isolated froma a patient in Huashan Hospital, Shanghai, China (2004)
  • Author(s): Zizhong, Xiong, Zhu, D., Wang, F., Zhang, Y., Okamoto, R., Inoue, M.
  • Journal Title: Int J Antimicrob 23 Pages: 262-267
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Antagonism between aminoglycosides and β-lactams in a methicillin-resistant Staphylococcus aureus isolates involves induction of an aminoglycoside-modifying enzyme (2003)
  • Author(s): Ida, T., R.Okamoto, M.Nonoyama, K.Irinoda, M.Kurazono, M.Inoue
  • Journal Title: Antimicrob Agents Chemother 1516-15222,2002 46 Pages: 1516-1522
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Production of macrophages inflammatory protein 3α (MIP-3α) (CC L20) and MIp-3β (CC L19) by human peripheral blood neurtropils in response to Microbial pathogens. (2003)
  • Author(s): Akaboshi, T., T.Sasahara, R.Namai, T.Matsui, H.Watanabe, H.Kitasato, M.Inoue, H.Kondo
  • Journal Title: Infect Immunity 71 Pages: 524-526
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Induction of telithromycin resistance in Streptococcus pneumoniae. (2003)
  • Author(s): Kaieda, S., N.Okitsu, H.Yano, H.Hosaka, R.Nakano, R.Okamoto, H.Takahashi, M.Inoue
  • Journal Title: J Antimicrob Chemother 50 Pages: 736-737
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Presumed endocarditis caused by BRO-β-lactamase producing M.catarrhalis in an infant with Fallot' sTetrad.,2003 (2003)
  • Author(s): Nagano, N., J.Sato, C.Cordevant, Y.Hagano, F.Taguchi, M.Inoue
  • Journal Title: J clin Microbiol 41 Pages: 5310-5312
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Production of macrophages inflammatory protein 3α(MIP-3α)(CC L20) and MIp-3β(CC L19) by human peripheral blood neurtropils in response to Microbial pathogens. (2003)
  • Author(s): Akaboshi, T., Sasahara, T.Namai, R., Matsui, T., Watanabe, H., Kitasato, H., Inoue, M., Kondo, H.
  • Journal Title: Infect Immunity 71 Pages: 524-526
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Retrovirally introduced prostaglantin D2 synthetase suppresses lung injury induced by bleomycin. (2003)
  • Author(s): Ando, M., Murakami, Y., Kojima, F., Endo, H., Kitasato, H., Hashimoto, A., Kobayashi, H., Majima, M., Inoue, M., Kondo, H., Kawai, S., Hayashi, I.
  • Journal Title: Am J Resp cell and Mol Biol 28 Pages: 582-591
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characteristic expression of three genes, msr(A), mph(C) and erm(Y) that confer resistance to macrolide antibiotics on Staphylo coccus aureus. (2003)
  • Author(s): Matsuoka, M., Inoue, M., Endo, Y., Nakajima, Y.
  • Journal Title: FEMS Microbial Lett 220 Pages: 287-293
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of telithromycin resistance in Streptococcus pneumoniae. (2003)
  • Author(s): Kaieda, S., Okitsu, N., Yano, U., Hosaka, H., Nakano, R., Okamoto, R., Takahashi, H., Inoue, M.
  • Journal Title: J Antimicrob Chemothe 50 Pages: 736-737
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Presumed enducarditis caused by BRO-β-lactamase Producing M. catarrhalis in an infant with Fallot' sTetrad. (2003)
  • Author(s): Nagano, N., Sato, J., Cordevant, C., Nagano, Y., Taguchi, F., Inoue, M.
  • Journal Title: J Clin Microbiol 41 Pages: 5310-5312
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Antiinflammatory effectt of retorovirally transfected interleukin-10 on monosodium urate monohydrate crystal-induced acute inflammation in murine air pouches. (2002)
  • Author(s): Murakami Y., T.Akaboshi, S.Kawai, M.Inoue, H.Kitasato
  • Journal Title: Arthritis & Rheumatism, 2002 46 Pages: 2504-2513
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of pKU701, a 2.5kb plasmid, in a Japanese Helico- bacter pyrori isolate. (2002)
  • Author(s): Hosaka, Y., R.Okamoto, K.Irinoda, S.Kaieda, W.Koizumi, K.Saigenji, M.Inoue
  • Journal Title: J.Antibiotics 50 Pages: 495-498
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Antagonism between aminoglycosides and β-lactams in a methicillin-resistant Staphylococcus aureus isolates involves induction of an aminoglycoside-modifying enzyme. (2002)
  • Author(s): Ida, T., Okamoto, R., Nonoyama, M., Irinoda, K., Kurazono, M., Inoue, M.
  • Journal Title: Antimicrob Agents Chemother 46 Pages: 1516-1521
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Antiinflammatory effect of retorovirally transfected interleukin-10 on monosodium urate monohydrate crystal-induced acute inflammation in murine air pouches. (2002)
  • Author(s): Murakami, Y., Akaboshi, T., Kawai, S., Inoue, M., Kitasato, H.
  • Journal Title: Arthritis & Rheumatism 46 Pages: 2504-2513
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of pKU701, a 2.5kb plasmid, in a Japanese Helico-bacter pyrori isolate. (2002)
  • Author(s): Hosaka, Y., Okamoto, R., Irinoda, K., Kaieda, S., Koizumi, W., Saigenji, K., Inoue, M.
  • Journal Title: Plasmid 47 Pages: 193-200
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Helicobacter pylori survive ampicillin treatment in the Remnant Stomach. (2002)
  • Author(s): Hosaka, Y., Okamoto, R., Irinoda, K., Kaieda, S., Koizumi, W., Saigenji, K., Inoue, M.
  • Journal Title: J.Antibiotics 5 Pages: 495-498
  • Description: 「研究成果報告書概要(欧文)」より