The role of whole genome sequencing in characterizing the mechanism of action of antituberculosis compounds: the case of para-amino salicylic acid

Para-aminosalicylic acid (PAS) was one of the first antibiotics to be used against tuberculosis and it is still one of the drugs of last resort available to treat extensively drug-resistant disease. Despite being on the market for decades, the mechanism of action of PAS is not completely understood. The main aim of this project was to identify new potential mechanisms of action of and resistance to PAS by performing whole genome sequencing (WGS) on PAS-resistant laboratory mutants.PAS resistant laboratory mutants of the Mycobacterium tuberculosis reference strain H37Rv were spontaneously selected and WGS analysis identified a total of 22 single nucleotide polymorphisms (SNPs) when compared with the reference strain. Variants in several genes previously associated with PAS resistance, e.g. folC and thyA, were identified with the PAS-resistant mutants.