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Inactivation mechanisms of antibiotic by pathogenic Nocardia and related taxa

致病性诺卡氏菌及相关类群对抗生素的灭活机制

基本信息

批准号：
06670284
负责人：
MIKAMI Yuzuru
金额：
$ 1.34万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670284/
关键词：
Nocandia acid-fast Antibiotic inactivation rifampicin glucosylation ribosylation Nocardia 病原性放線菌

项目摘要

We had reported that pathogenic Nocardia showed species-specific resistant patterns against macrolide antibiotics and rifampicin. A survey of five Nocardia spp. with respect to susceptibility towards three macrolides (erythromycin, rokitamycin and midecemycin) showed that the Nocardia spp. have different susceptibility profiles. Most of the resistance was due to the inactivation of the macrolides by phosphorylation, glucosylation, reduction and deacylation, or combination of there of. The studies on the rifampicin inactivation showed that rifampicin was inactivated by phosphorylation and glucosylation. In addition, we also find a new inactivation mechanism in other acid-fast bacterium such as Mycobacterium. Severalfast-growing Mycobacterium strains were found to inactivate rifampicin. Two inactivated compounds produced by these organisms were different from previously reported derivatives, i. e., phosphorylated or glucosylated derivatives of the antibiotic. The structures of two compounds were determined to be those of 3-formyl-23-[O-alpha-D-ribafuranosyl]rifamycin SV and 23-[O-(alpha-D-ribofuranosyl)]rifampicin, respectively. To our knowledge, this is the first known examples of ribosylation as a mechanism of antibiotic inactivation. Our recent studies indicated that NADH is a essential for the ribosylation as a substrate. We also obtained two possible intermediate compounds which lead to ribosylation and their molecular weights were found to be 1034 and 1363, respectively. Now detail studies on the gene (s) associated with ribosylation activity and structural determination of the intermediates are progress.

本文报道了致病性诺卡氏菌对大环内酯类抗生素和利福平的耐药模式。对5种诺卡氏菌进行了调查。对3种大环内酯类抗生素（红霉素、罗他霉素和麦迪霉素）的敏感性试验表明，诺卡氏菌属（Nocardia spp.）具有不同的磁化率分布。大多数耐药性是由于大环内酯类通过磷酸化、糖基化、还原和脱酰化或其组合而失活。对利福平失活的研究表明，磷酸化和糖基化使利福平失活。此外，我们还发现了其他抗酸菌如分枝杆菌的一种新的失活机制。几种快速生长的分枝杆菌菌株对利福平有抗药性。由这些微生物产生的两种失活化合物不同于以前报道的衍生物，即。例如，抗生素的磷酸化或葡糖基化衍生物。两个化合物的结构分别确定为3-甲酰基-23-[O-α-D-呋喃核糖基]利福霉素SV和23-[O-（α-D-呋喃核糖基）]利福平。据我们所知，这是第一个已知的核糖基化作为抗生素失活机制的例子。我们最近的研究表明，NADH作为底物是核糖基化所必需的。我们还得到了两个可能的中间体化合物，导致核糖基化，其分子量分别为1034和1363。目前，对核糖基化活性相关基因的研究以及中间产物的结构鉴定都取得了进展。