1995 Fiscal Year Final Research Report Summary
Inactivation mechanisms of antibiotic by pathogenic Nocardia and related taxa
| Project/Area Number |
06670284
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Chiba University |
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Principal Investigator |
MIKAMI Yuzuru Chiba Uni. Res. Cent. Patho. Fungi and Microb. Toxicoses, Div. of Chemother. Associate Prof., 真核微生物研究センター, 助教授 (40092100)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Nocandia / acid-fast / Antibiotic / inactivation / rifampicin / glucosylation / ribosylation |
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| Research Abstract |
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.
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