Mutations inandInterogenic Region in Isoniazid-ResistantClinical Isolates from Chongqing, China.

BACKGROUND AND AIM: As a first line anti-tuberculosis drug, isoniazid (INH) has been extensively used for decades. Consequently, resistance of(MTB) clinical isolates to INH is inevitably increasing and spreading, necessitating fast and accurate molecular diagnosis tools. Although many previous molecular epidemiological studies related with INH resistance included mutations in theintergenic region, the role of mutations in theintergenic region in INH resistance remains controversial. The present study aimed to investigate the frequency and distribution of mutations in theand theintergenic region among INH-resistant(MTB) clinical isolates in Chongqing, China.

METHODS: The presence of mutations inand theintergenic region was analyzed in 490 MTB clinical isolates.

RESULTS: None of the 73 INH-susceptible isolates (0%), 18 of 26 INH mono-resistant isolates (69.2%), 188 of 199 MDR (multidrug resistant) isolates (94.5%), and 176 of 192 pre-XDR/XDR (pre-extensively drug-resistant) isolates (91.7%) had mutations in. No mutations inand theintergenic region were identified in INH-susceptible and INH mono-resistant isolates. Mutations in theintergenic region were rare (1.5% MDR, 1.04% pre-XDR), and only two mutations were identified (-58 G→A in MDR and -54 C→T in pre-XDR isolates). The former occurred in isolates with concurrentmutations, but the latter occurred in isolates without concurrentmutations. Notably, a novel Ala18Gly mutation inwas identified in 3.52% of MDR and 6.77% of pre-XDR isolates.

CONCLUSION: Mutation inis the main cause of INH resistance in MTB clinical strains isolated from Chongqing. It is very unlikely that mutation in theintergenic region alone could cause INH resistance in MTB clinical isolates. Even though mutation in theintergenic region could compensate the fitness cost ofmutation, our finding that it is uncommon in MTB clinical isolates from Chongqing suggests it is not the primary compensatory mechanism. Further investigation is necessary to probe the relationship between mutations in the coding region ofand INH resistance.