Distribution of Common and Rare Genetic Markers of Second-Line-Injectable-Drug Resistance in Mycobacterium tuberculosis Revealed by a Genome-Wide Association Study

Author:

Conkle-Gutierrez Derek1ORCID,Kim Calvin1,Ramirez-Busby Sarah M.1,Modlin Samuel J.1ORCID,Mansjö Mikael2,Werngren Jim2,Rigouts Leen34,Hoffner Sven E.15,Valafar Faramarz1ORCID

Affiliation:

1. Laboratory for Pathogenesis of Clinical Drug Resistance and Persistence (LPCDRP), Biomedical Informatics Research Center, Division of Epidemiology, School of Public Health, San Diego State University, San Diego, California, USA

2. Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden

3. Department of Biomedical Sciences, Antwerp University (UA), Antwerp, Belgium

4. Mycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine (ITM), Antwerp, Belgium

5. Department of Global Public Health, Karolinska Institute, Stockholm, Sweden

Abstract

Point mutations in the rrs gene and the eis promoter are known to confer resistance to the second-line injectable drugs (SLIDs) amikacin (AMK), capreomycin (CAP), and kanamycin (KAN). While mutations in these canonical genes confer the majority of SLID resistance, alternative mechanisms of resistance are not uncommon and threaten effective treatment decisions when using conventional molecular diagnostics.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference64 articles.

1. World Health Organization. 2021. Global tuberculosis report 2021. World Health Organization, Geneva, Switzerland.

2. World Health Organization. 2019. Global tuberculosis report 2019. Document number WHO/CDS/TB/2019.15. World Health Organization, Geneva, Switzerland.

3. World Health Organization. 2014. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Document number WHO/HTM/TB/2014.11. World Health Organization, Geneva, Switzerland.

4. Drug Resistance Mechanisms in Mycobacterium tuberculosis

5. Comparison of clinical isolates and in vitro selected mutants reveals that tlyA is not a sensitive genetic marker for capreomycin resistance in Mycobacterium tuberculosis

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