Coresistance to Isoniazid and Ethionamide Maps to Mycothiol Biosynthetic Genes in Mycobacterium bovis

A search to identify new mechanisms of isoniazid resistance in Mycobacterium bovis led to the isolation of mutants defective in mycothiol biosynthesis due to mutations in genes coding for the glycosyltransferase (mshA) or the cysteine ligase (mshC). These mutants showed low-level resistance to isoniazid but were highly resistant to ethionamide. This study further illustrates that mutations in mycothiol biosynthesis genes may contribute to isoniazid or ethionamide resistance across mycobacterial species. Drug resistance in Mycobacterium tuberculosis has been a growing concern since the introduction of the first chemother-apy for tuberculosis (TB). Resistance to the first-line antitu-berculosis drug isoniazid (INH) emerged less than a year after its introduction as a new TB drug in 1952 (8, 10). Now, almost one-third of new TB patients are infected with an INH-resis-tant (INHr) TB strain. Determination of all the factors causing INH resistance would be a tremendous help in the diagnosis of drug resistance, which would then lead to proper treatment for TB patients. In a recent study, almost 20 % of INHr clinica