Role of an RNA polymerase interacting protein, MsRbpA, from Mycobacterium smegmatis in phenotypic tolerance to rifampicin.
Rifampicin and its derivatives are at the forefront of the current standard chemotherapeutic regimen for active tuberculosis; they act by inhibiting the transcription activity of prokaryotic RNA polymerase. Rifampicin is believed to interact with the beta subunit of RNA polymerase. However, it has been observed that protein-protein interactions with RNA polymerase core enzyme lead to its reduced susceptibility to rifampicin. This mechanism became more diversified with the discovery of RbpA, a novel RNA polymerase-binding protein, in Streptomyces coelicolor that could mitigate the effect of rifampicin on RNA polymerase activity. MsRbpA is a homologue of RbpA in Mycobacterium smegmatis. On deciphering the role of MsRbpA in M. smegmatis we found that it interacts with RNA polymerase and increases the rifampicin tolerance levels, both in vitro and in vivo. It interacts with the beta subunit of RNA polymerase. However, it was found to be incapable of rescuing rifampicin-resistant RNA polymerases in the presence of rifampicin at the respective IC(50).
Dey
Abhinav
A
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Verma
Amit Kumar
AK
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Chatterji
Dipankar
D
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D003432:Cross-Linking Reagents; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D003432:Cross-Linking Reagents; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin