Light inhibits rifampicin inactivation and reduces rifampicin resistance due to a cloned mycobacterial ADP-ribosylation gene.
Rifampicin is a principal drug used to combat infections by mycobacteria and related organisms. Most strains of Mycobacterium are able to inactivate this antibiotic by ribosylation via an ADP-ribosylated intermediate. We found that this inactivation was inhibited by light at levels similar to those prevailing in laboratory environments. Rifampicin resistance arising from the cloned ADP-ribosyl transferase was also greatly diminished at these light levels. The cloned Rhodococcus equi monooxygenase which inactivates this antibiotic by a different mechanism was, in contrast, not inhibited by light.
Dabbs
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Department of Molecular and Cell Biology, University of the Witwatersrand, P.O. WITS 2050, Witwatersrand, South Africa. 108eric@cosmos.wits.ac.za
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D000904:Antibiotics, Antitubercular / Q000378:metabolism* / Q000494:pharmacology; D003001:Cloning, Molecular; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D008027:Light; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D010105:Oxygenases / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D012240:Rhodococcus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D016929:Rhodococcus equi / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D012293:Rifampin / Q000378:metabolism* / Q000494:pharmacology
D000904:Antibiotics, Antitubercular; D010105:Oxygenases; D011065:Poly(ADP-ribose) Polymerases; D012293:Rifampin