INH Direnç Mekanizmaları

Her ne kadar izoniazid (INH) 'ın Mycobacterium tuberculosis üzerindeki etki mekanizması tam anlaşılamamış olsa da öncü ilaç olan INH sitoplazmaya pasif difüzyon ile girmektedir. KatG geni tarafından kodlanan katalaz/peroksidaz enzimi ile aktiflenmektedir. INH 'ın aktiflenmesi ile serbest metabolik radikaller oluşmakta, bunlar da mikolik asit sentezi gibi pek çok hücresel fonksiyonu bozmaktadırlar. KatG mutasyonları INH direncinin ana sebebidir. INH 'a dirençli klinik izolatların % 50 'den fazlasında katG 315. pozisyonda serin yerine treonin 'in değiştiği bir mutasyon vardır. İnhA, ndh ve pompa genleri gibi genler de INH direncine katkıda bulunabilirler. Bu derleme yazısı Mycobacterium tuberculosis 'de INH etki mekanizmasını ve ilaç direncinin moleküler temellerini özetlemektedir.

INH Resistance Mechanisms

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.

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