Kiran Chawla1, Elena Martinez2, Ajay Kumar1, Vishnu Prasad Shenoy1, Vitali Sintchenko3. 1. Department of Microbiology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India. 2. Centre for Infectious Diseases and Microbiology, Level 3 ICPMR Building, Westmead Hospital, Wentworthville, NSW 2145, Australia. 3. Centre for Infectious Diseases and Microbiology, Level 3 ICPMR Building, Westmead Hospital, Wentworthville, NSW 2145, Australia. Electronic address: vitali.sintchenko@sydney.edu.au.
Abstract
OBJECTIVES: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has opened up new challenges for tuberculosis (TB) control in India. This study examined molecular markers of resistance to bedaquiline, a new antituberculous drug with the potential to dramatically improve MDR-TB treatment outcomes and to reduce mortality. METHODS: A clinical M. tuberculosis isolate with a MDR-TB profile was subjected to whole-genome sequencing using an Illumina NextSeq500 platform, followed by genome-wide sequence analysis. RESULTS: A mutation in the Rv0678 coding region associated with in vitro bedaquiline resistance was identified. The strain represented the Delhi/CAS lineage. CONCLUSIONS: This first report of a potentially bedaquiline-resistant M. tuberculosis strain in India highlights the role of genome-wide sequence analysis of isolates from TB cases with a history of treatment in countries with a high burden of MDR-TB and XDR-TB.
OBJECTIVES: The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has opened up new challenges for tuberculosis (TB) control in India. This study examined molecular markers of resistance to bedaquiline, a new antituberculous drug with the potential to dramatically improve MDR-TB treatment outcomes and to reduce mortality. METHODS: A clinical M. tuberculosis isolate with a MDR-TB profile was subjected to whole-genome sequencing using an Illumina NextSeq500 platform, followed by genome-wide sequence analysis. RESULTS: A mutation in the Rv0678 coding region associated with in vitro bedaquiline resistance was identified. The strain represented the Delhi/CAS lineage. CONCLUSIONS: This first report of a potentially bedaquiline-resistant M. tuberculosis strain in India highlights the role of genome-wide sequence analysis of isolates from TB cases with a history of treatment in countries with a high burden of MDR-TB and XDR-TB.
Authors: Svetlana G Frolova; Ksenia M Klimina; Ravinder Kumar; Aleksey A Vatlin; Deepak B Salunke; Pravin Kendrekar; Valery N Danilenko; Dmitry A Maslov Journal: Antibiotics (Basel) Date: 2020-12-23
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