Elucidating isoniazid resistance using molecular
Intrinsic drug resistance of has traditionally been attributed to the unusual structure of its mycolic acid-containing cell wall that gives the bacteria a low permeability for many compounds such as antibiotics and other chemotherapeutic agents.More recently, the role of efflux mechanisms has also been recognized as an important factor in the natural resistance of mycobacteria against antibiotics such as tetracycline, fluoroquinolones and aminoglycosides, among others.
With the discovery of several other drugs with anti-TB activity, multidrug therapy became fundamental for the control of the disease by promoting the cure of the patients and interrupting the chain of transmission.
This could be partially explained by the hypothesis that -acetyltransferase protein appears to play an important role in the synthesis of the mycobacterial cell wall in slow-growing mycobacteria and has been suggested to be a target for anti-mycobacterial therapy.
in 8.9% of 224 isoniazid-resistant strains studied, confirming its less frequent involvement as a cause of resistance to isoniazid.
Very early on, it was also shown that have been reported, with MICs ranging from 0.2 to 256 mg/L.
Missense and nonsense mutations, insertions, deletions, truncation and, more rarely, full gene deletion have been observed.