INH Direnç Mekanizmaları

• Main Authors: Tanseli Gönlügür, Ugur Gönlügü
• Format: Article
• Language: English
• Published: Dicle University Medical School 2017-09-01
• Series: Dicle Medical Journal
• Subjects: Isoniazid; resistance; mechanisms; tuberculosis
• Online Access: http://diclemedj.org/upload/sayi/65/Dicle%20Med%20J-03257.PDF

Although the precise mechanism of isoniazid (INH) action on Mycobacterium tuberculosis remains poorly understood, the pro-drug INH enters the cytoplasm through simple passive diffusion. It activated by the enzyme catalase/peroxidase encoded by KatG gene. Activation of INH results in the formation of various potent free radical species that are capable of disabling many cellular processes such as mycolic acid synthesis. Mutations in katG are the major mechanism of INH resistance. More than 50% of isoniazid-resistant clinical isolates contain a mutation in KatG wherein the serine at position 315 is substituted with threonine. Several other genes such as inhA, ndh, and efflux pump genes may contribute to INH resistance. This review article discusses the mechanisms of action of INH and the molecular basis of drug resistance in M. tuberculosis.