Andersen SJ, Quan S, Dabbs ER; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18; 52 (abstract no. C103).
University of the Witwatersrand, Johannesburg, South Africa.
Rifampin is one of the principal chemotherapeutic agents used to combat infections by species of Mycobacterium, Nocardia, and Rhodococcus. Recently it has been demonstrated that part of the response of these organisms to challenge with this antibiotic involves an inactivation process. Four mechanisms have been identified: phosphorylation, glucosylation, ribosylation, or decomposition of rifampin. We have cloned the DNA responsible for one of these inactivation mechanisms from Rhodococcus equi, a pathogen of foals and now also infecting immunocompromised human. The gene responsible conferred the ability to decompose rifampin, resulting in its decolorization. Introduced into a rhodococcal strain unable to inactivate this antibiotic, it increased resistance over twenty-fold. Expression of a delta promoter resulted in greater than ten-fold increase in rifampin resistance in Escherichia coli. The gene was on a 2 kb BcII-ClaI fragment, within which an open reading frame of 1438 bp was found coding for a polypeptide of 479 residues. BLAST programs were used to search for significant sequence similarities; high scores were obtained with genes coding for monooxygenases/hydroxylases which act upon phenolic compounds, consistent with the structure of the aromatic portion of the rifampin molecule.
Publication Types:
Keywords:
- Anti-Bacterial Agents
- Antibiotics, Antitubercular
- Base Sequence
- Escherichia coli
- Humans
- Mixed Function Oxygenases
- Mycobacterium
- Rhodococcus
- Rhodococcus equi
- Rifampin
- genetics
Other ID:
UI: 102234780
From Meeting Abstracts