Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 16906155.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Isoniazid is one of the most effective antituberculosis drugs, yet its precise mechanism of action is still controversial. Using specialized linkage transduction, a single point mutation allele (S94A) within the putative target gene inhA was transferred in Mycobacterium tuberculosis. The inhA(S94A) allele was sufficient to confer clinically relevant levels of resistance to isoniazid killing and inhibition of mycolic acid biosynthesis. This resistance correlated with the decreased binding of the INH-NAD inhibitor to InhA, as shown by enzymatic and X-ray crystallographic analyses, and establishes InhA as the primary target of isoniazid action in M. tuberculosis.
Medical subject headings
- Bacterial Proteins
- Isoniazid
- Mycobacterium tuberculosis
- Oxidoreductases
- Point Mutation