Journal article

Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae

SC Vedithi, S Malhotra, M Das, S Daniel, N Kishore, A George, S Arumugam, L Rajan, M Ebenezer, DB Ascher, E Arnold, TL Blundell

Scientific Reports | Published : 2018

Abstract

The rpoB gene encodes the β subunit of RNA polymerase holoenzyme in Mycobacterium leprae (M. leprae). Missense mutations in the rpoB gene were identified as etiological factors for rifampin resistance in leprosy. In the present study, we identified mutations corresponding to rifampin resistance in relapsed leprosy cases from three hospitals in southern India which treat leprosy patients. DNA was extracted from skin biopsies of 35 relapse/multidrug therapy non-respondent leprosy cases, and PCR was performed to amplify the 276 bp rifampin resistance-determining region of the rpoB gene. PCR products were sequenced, and mutations were identified in four out of the 35 cases at codon positions D44..

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University of Melbourne Researchers

Grants

Awarded by Fundação de Amparo à Pesquisa do Estado de Minas Gerais


Funding Acknowledgements

We thank Dr. Bernardo Ochoa for his suggestions and discussions on mapping interatomic interactions. We thank the director, administrative and research staff of SIH-R&LC Karigiri for the infrastructural and financial support to conduct experiments. We acknowledge the contributions of clinical and support staff at the Father Muller Foundation, Mangalore and Government Medical College, Trivandrum for clinical assessment of relapse and MDT-non-respondent leprosy cases and shipment of samples. SCV was supported by American leprosy Missions Grant (G88726); TLB was supported by the Wellcome Trust Programme Grant (200814/Z/16/Z); SM was supported by the MRC Newton Award (RG78439). DBA was funded by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (MR/M026302/1).