Role of Whole-Genome Sequencing in Characterizing the Mechanism of Action of para-Aminosalicylic Acid and Its Resistance

Giovanni Satta; Adam A Witney; Neelu Begum; Julio Ortiz Canseco; Andrew N Boa; Timothy D McHugh

doi:10.1128/AAC.00675-20

Role of Whole-Genome Sequencing in Characterizing the Mechanism of Action of para-Aminosalicylic Acid and Its Resistance

Antimicrob Agents Chemother. 2020 Aug 20;64(9):e00675-20. doi: 10.1128/AAC.00675-20. Print 2020 Aug 20.

Authors

Giovanni Satta^{1

2}, Adam A Witney³, Neelu Begum⁴, Julio Ortiz Canseco⁴, Andrew N Boa⁵, Timothy D McHugh⁴

Affiliations

¹ Centre for Clinical Microbiology, University College London, London, United Kingdom giovanni.satta@nhs.net.
² Department of Infectious Disease, Imperial College London, London, United Kingdom.
³ Institute for Infection and Immunity, St. George's University of London, London, United Kingdom.
⁴ Centre for Clinical Microbiology, University College London, London, United Kingdom.
⁵ Department of Chemistry, University of Hull, Hull, United Kingdom.

Abstract

para-Aminosalicylic acid (PAS) remains one of the drugs of last resort for the treatment of tuberculosis, but its mechanism of action is still not completely understood. The main aim of this project was to identify new potential mechanisms of action and resistance to PAS by performing whole-genome sequencing on PAS-resistant laboratory mutants. A new variant in the folC gene was identified, as well as some other mutations that require further study.

Keywords: para-aminosalicylic acid; tuberculosis; whole-genome sequencing.

MeSH terms

Aminosalicylic Acid* / pharmacology
Drug Resistance, Bacterial / genetics
Microbial Sensitivity Tests
Mycobacterium tuberculosis* / genetics
Whole Genome Sequencing

Substances

Aminosalicylic Acid

Grants and funding

MR/T023686/1/MRC_/Medical Research Council/United Kingdom