2003 Fiscal Year Annual Research Report

黄色ブドウ球菌の全ゲノム情報に基づく薬剤耐性機構の解明とその克服

Research Project

Project/Area Number	14021113
Research Institution	Juntendo University
Principal Investigator	平松啓一順天堂大学, 医学部, 教授 (10173262)
Keywords	ゲノム / 黄色ブドウ球菌 / 耐性遺伝子 / 抗生物質 / DNAアレイ / トランスクリプトーム / MRSA / バンコマイシン
Research Abstract	黄色ブドウ球菌全ゲノム遺伝子のMicroarrayを用いて、vancomycin耐性、methicillin高度耐性を示す黄色ブドウ球菌臨床分離株Mu50,MC (Michigan, USA),NJ (New Jersey, USA),ら7株と、それらから作製したvancomycin感受性、methicillin感受性変異株Mu50S, MCS, NJS, etc7株との間で、transcription profileを比較解析した結果、これらの組み合わせのうち5例以上共通して転写量が(耐性菌において)増加が見られた遺伝子を126見いだした。それらをすべてプラスミドにクローン化し、vancomycin/methicillin感受性株N315に導入し、vancomycin、methicillinの耐性が増加するものを16見いだした。そのうち8個は従来知られていない遺伝子であった。その転写の更新がbeta-lactam高度耐性をもたらすとともにteicoplaninの耐性、vancomycinのhetero耐性をもたらすtwo-component system vraSRの機能を確定することに成功した。このシステムは、種々の細胞壁合成阻害薬の作用によって誘導され、その結果細胞壁合成酵素transglycosylase (SgtB),transpeptidase (PBP2)などの遺伝子の転写を促進する。すなわち、このsignal伝達系は、環境の変化に反応して細胞壁の合成を加速するgearのような役割を果たすシステムであることが推定された。このtwo-component systemをknockoutすることにより、glycopeptideの耐性が消失し、とくにteicopaninに対して、一般の感受性菌よりも高い感受性、すなわち超感受性となることが明らかになった。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Ito, T., et al.: "Insights on Antibiotic Resistance of Staphylococcus aureus from its Whole Genome : Genomic Island SCC"Drug Res.Updates. 6. 41-52 (2003)
[Publications] Cui, L., et al.: "Cell Wall Thickening Is a Common Feature of Vancomycin Resistance in Staphylococcus aureus"J.Clin.Microbiol.. 41. 5-14 (2003)
[Publications] Yoshida, R., et al.: "Physiological and molecular analysis of a mecA-negative Staphylococcus aureus clinical strain that expresses heterogeneous methicillin resistance"J Antimicrob Chemother. 51. 247-255 (2003)
[Publications] Katayama, Y., et al.: "Identification in a methicillin-susceptible Staphylococcus hominis of an active primordial mobile genetic element for the staphylococcal cassette chromosome mec (SCCmec) of methicillin-resistant Staphylococcus aureus."J.Bacteriol.. 185. 2711-2722 (2003)
[Publications] Isnansetyo, A., et al.: "Antibacterial activity of 2,4-diacetylphloroglucinol (DAPG) produced by Pseudomonas sp. AMSN isolated from a marine alga, against vancomycin-resistant Staphylococcus aureus (VRSA)"Int J Antimicrob Agents. 22. 545-547 (2003)
[Publications] Kuroda, M., et al.: "Two-component system VraSR positively modulates the regulation of cell wall biosynthesis pathway in Staphylococcus aureus"Molecular Microbiol. 49. 807-821 (2003)
[Publications] Cui, L.et al.: "Vancomycin-resistant Staphylococcus aureus."Horizon Scientific Press. 340 (2003)
[Publications] Kuroda, M. et al.: "Genomics, Proteomics and Clinical Bacteriology."Humana Press. 320 (2004)
[Publications] Baba, T. et al.: "The Genome of Staphylococcus aureus."Eliis Harwood (In press). (2004)
[Publications] Hiramatsu, K.: "Elucidation of the mechanism of antibiotic resistance acquisition of methicillin-resistant Staphylococcus aureus (MRSA) and determination of its whole genome nucleotide sequence"Jap Med Assoc J. (In press). (2004)
[Publications] Hiramatsu, K., et al.: "The Staphylococcus aureus model"ASM Press (In Press). (2004)

2003 Fiscal Year Annual Research Report

黄色ブドウ球菌の全ゲノム情報に基づく薬剤耐性機構の解明とその克服

Principal Investigator

平松 啓一 順天堂大学, 医学部, 教授 (10173262)

Research Products

[Publications] Ito, T., et al.: "Insights on Antibiotic Resistance of Staphylococcus aureus from its Whole Genome : Genomic Island SCC"Drug Res.Updates. 6. 41-52 (2003)

[Publications] Cui, L., et al.: "Cell Wall Thickening Is a Common Feature of Vancomycin Resistance in Staphylococcus aureus"J.Clin.Microbiol.. 41. 5-14 (2003)

[Publications] Yoshida, R., et al.: "Physiological and molecular analysis of a mecA-negative Staphylococcus aureus clinical strain that expresses heterogeneous methicillin resistance"J Antimicrob Chemother. 51. 247-255 (2003)

[Publications] Katayama, Y., et al.: "Identification in a methicillin-susceptible Staphylococcus hominis of an active primordial mobile genetic element for the staphylococcal cassette chromosome mec (SCCmec) of methicillin-resistant Staphylococcus aureus."J.Bacteriol.. 185. 2711-2722 (2003)

[Publications] Isnansetyo, A., et al.: "Antibacterial activity of 2,4-diacetylphloroglucinol (DAPG) produced by Pseudomonas sp. AMSN isolated from a marine alga, against vancomycin-resistant Staphylococcus aureus (VRSA)"Int J Antimicrob Agents. 22. 545-547 (2003)

[Publications] Kuroda, M., et al.: "Two-component system VraSR positively modulates the regulation of cell wall biosynthesis pathway in Staphylococcus aureus"Molecular Microbiol. 49. 807-821 (2003)

[Publications] Cui, L.et al.: "Vancomycin-resistant Staphylococcus aureus."Horizon Scientific Press. 340 (2003)

[Publications] Kuroda, M. et al.: "Genomics, Proteomics and Clinical Bacteriology."Humana Press. 320 (2004)

[Publications] Baba, T. et al.: "The Genome of Staphylococcus aureus."Eliis Harwood (In press). (2004)

[Publications] Hiramatsu, K.: "Elucidation of the mechanism of antibiotic resistance acquisition of methicillin-resistant Staphylococcus aureus (MRSA) and determination of its whole genome nucleotide sequence"Jap Med Assoc J. (In press). (2004)

[Publications] Hiramatsu, K., et al.: "The Staphylococcus aureus model"ASM Press (In Press). (2004)

平松啓一順天堂大学, 医学部, 教授 (10173262)