Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

12 January 2024 | The CRyPTIC Consortium*
This study aimed to develop a quantitative catalog of antibiotic resistance in *Mycobacterium tuberculosis* (Mtb) by combining whole-genome sequencing (WGS) with high-throughput minimum inhibitory concentration (MIC) measurements. The researchers analyzed 15,211 clinical isolates from 23 countries across five continents, focusing on 13 drugs. They identified 492 unique mutations associated with elevated MICs and 91 mutations linked to hypersensitivity. The findings advance genetics-based diagnostics for tuberculosis and provide a curated dataset for developing drug resistance prediction algorithms. The study highlights the importance of considering sub-threshold elevations in MICs, which can be clinically significant and underdiagnosed. It also identifies mutations associated with increased susceptibility to newer drugs like bedaquiline, clofazimine, and aminoglycosides, suggesting potential for optimizing treatment regimens. The catalog can be used to improve diagnostics and guide future studies on high-dose therapies for less toxic and more effective drugs. However, the study acknowledges limitations, including the lower number of isolates resistant to newer drugs and the need for further validation of MICs against other methods.This study aimed to develop a quantitative catalog of antibiotic resistance in *Mycobacterium tuberculosis* (Mtb) by combining whole-genome sequencing (WGS) with high-throughput minimum inhibitory concentration (MIC) measurements. The researchers analyzed 15,211 clinical isolates from 23 countries across five continents, focusing on 13 drugs. They identified 492 unique mutations associated with elevated MICs and 91 mutations linked to hypersensitivity. The findings advance genetics-based diagnostics for tuberculosis and provide a curated dataset for developing drug resistance prediction algorithms. The study highlights the importance of considering sub-threshold elevations in MICs, which can be clinically significant and underdiagnosed. It also identifies mutations associated with increased susceptibility to newer drugs like bedaquiline, clofazimine, and aminoglycosides, suggesting potential for optimizing treatment regimens. The catalog can be used to improve diagnostics and guide future studies on high-dose therapies for less toxic and more effective drugs. However, the study acknowledges limitations, including the lower number of isolates resistant to newer drugs and the need for further validation of MICs against other methods.
Reach us at info@study.space