Mutations Found inembCAB,embR, andubiAGenes of Ethambutol-Sensitive and -ResistantMycobacterium tuberculosisClinical Isolates from China

Abstract

To better understand the molecular mechanisms of Ethambutol (EMB) resistance, the mutant hot spot region of five genes (embB, embA, embC, embR, andubiA) was amplified and sequenced in 109 EMB-resistant and 153 EMB-susceptible clinical isolates from China. Twenty-seven EMB-susceptible isolates were found to have nonsynonym mutations, 23 of which were inembB. The mutations occurred most frequently inembB(85.3%, 93) and were seldom inembC(2.8%, 3),embA(3.7%, 4),embR(3.7%, 4), andubiA(8.3%, 9) in EMB-resistant isolates. For theembBgene, 63 isolates showed mutations atembB306, 20 atembB406, nine atembB497, and five atembB354 in EMB-resistant isolates. In addition, the particular mutants atembB406 andembB497 indicated both high levels of EMB resistance (MICs>5 μg/mL) and broad anti-TB drug resistance spectrums. Our data supported the facts thatembB306 could be used as a marker for EMB resistance with a sensitivity of 57.8% and a specificity of 78.8%.