SETTING: The incidence of tuberculosis as well as drug resistance in Italy is low as compared to other countries. Isoniazid is a frontline drug for the treatment of tuberculosis. Mutations in several genes and genomic regions of Mycobacterium tuberculosis are involved in the occurrence of isoniazid resistance. OBJECTIVE: To investigate the mutations responsible for isoniazid resistance of M. tuberculosis strains isolated in Italy, in order to assess the feasibility of prediction of drug resistance by a genetic approach. DESIGN: The mutations responsible for INH resistance were searched in selected regions of genes katG, kasA and ndh and in the promoter regions of inhA and ahpC by nucleotide sequencing, and the results were compared with data reported in other studies. RESULTS: Prevalent isoniazid-resistance mutations were found at codon 315 of katG gene and at position -15 of inhA regulatory region (37.8% and 20.0% of isolates, respectively). Prevalence of mutations at position -24 of inhA, in ahpC, and in kasA ranged from 2.2% to 4.4%. No mutations were found in 35.6% of the isolates. CONCLUSION: The identification of isoniazid resistance by genetic analysis of selected regions of katG, inhA, ahpC, kasA and ndh may be inappropriate in areas with low prevalence of tuberculosis, such as Italy, as the genetic mechanisms of resistance remain unidentified for approximately one third of the isolates.
Mutations responsible for Mycobacterium tuberculosis isoniazid resistance in Italy
RINDI, LAURA;GARZELLI, CARLO;
2005-01-01
Abstract
SETTING: The incidence of tuberculosis as well as drug resistance in Italy is low as compared to other countries. Isoniazid is a frontline drug for the treatment of tuberculosis. Mutations in several genes and genomic regions of Mycobacterium tuberculosis are involved in the occurrence of isoniazid resistance. OBJECTIVE: To investigate the mutations responsible for isoniazid resistance of M. tuberculosis strains isolated in Italy, in order to assess the feasibility of prediction of drug resistance by a genetic approach. DESIGN: The mutations responsible for INH resistance were searched in selected regions of genes katG, kasA and ndh and in the promoter regions of inhA and ahpC by nucleotide sequencing, and the results were compared with data reported in other studies. RESULTS: Prevalent isoniazid-resistance mutations were found at codon 315 of katG gene and at position -15 of inhA regulatory region (37.8% and 20.0% of isolates, respectively). Prevalence of mutations at position -24 of inhA, in ahpC, and in kasA ranged from 2.2% to 4.4%. No mutations were found in 35.6% of the isolates. CONCLUSION: The identification of isoniazid resistance by genetic analysis of selected regions of katG, inhA, ahpC, kasA and ndh may be inappropriate in areas with low prevalence of tuberculosis, such as Italy, as the genetic mechanisms of resistance remain unidentified for approximately one third of the isolates.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
