アクティブボード・２０１６年１２月
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研究発表を行った学会；
・The 13th Korea-Japan International Symposium on Microbiology
　　2016年5月12日〜13日（Gyeongju, Korea）

タイトル；Desensitization by Penicillin Binding Protein 5 (PBP5) Against β-lactam antibiotics via Formation of Cysteinyl-β-lactam-protein adducts.
発表者；小野　勝彦　氏
　　　（熊本大学　大学院生命科学研究部　微生物学分野）
要旨；
[Aim of this study] Recent study showed that antibiotic treatments stimulate the production of reactive oxygen spices in Gram-negative and Gram-positive bacteria, regardless of specific drug targets. In the process of analyzing the redox state of antibiotics treated bacteria, we found that β-lactam antibiotics were rapidly inactivated in the presence of cysteine. In this study, we investigated molecular mechanisms for cysteine-mediated inactivation of β-lactam and their implications in bacterial β-lactam responses.
[Methods] Anti-bacterial activities of cysteine-treated β-lactams were tested by disk dilution method. Protein modification by β-lactams were analyzed by means of Western blotting with newly generated anti-β-lactam antibody as well as by mass spectrum-based proteomics.
[Results] Ampicillin and meropenem readily reacted with cysteine to form cystenyl-β-lactam adducts. These adducts were no longer bacteriocidal. Furthermore, cysteinyl-meropenem protein adducts were determined in meropenem treated E.coli cells. Proteomic analyses revealed that penicillin binding protein 5 and 6a (PBP5 and PBP6a) were susceptible targets for the S-meropenem modification in E.coli. PBP5-deficient E.coli become more sensitive to β-lactam antibiotics compared with wild type. These findings suggest the novel function of PBP5 to desensitive bacteria against β-lactam antibiotics, and warrant further investigation to develop chemotherapies targeting PBP5 functions.

Key words
β-lactam antibiotics, cysteine, proteomics, penicillin binding protein, meropenem