Abstract
As the causative bacteria of tuberculosis, Mycobacterium tuberculosis (M. tb) is aggravated by the emergence of its multidrug-resistant isolates in China. Mutations of six of the most frequently reported resistant genes (rpoB, katG, inhA, embB, gyrA, and rpsL) were detected for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), ofloxacin (OFX), and streptomycin (STR) in this study. The amino acid missense mutations (MMs) and their corresponding single nucleotide polymorphism mutations for all drug-resistant (DR) isolates are described in detail. All isolates were divided into non-extensively drug-resistant (Non-XDR) and preXDR/XDR groups. No statistical differences were detected among MMs and linked MMs (LMs) between the two groups, except for rpsL 88 (p = 0.037). In the preXDR/XDR group, the occurrence of MMs in rpoB, katG, and inhA developed phenotypic resistance and MMs of rpoB 531, katG 315, rpsL 43, and rpsL 88 could develop high levels of DR. It is necessary to carry out epidemiological investigations of DR gene mutations in the local region, and thus provide necessary data to support the design of new technologies for rapid detection of resistant M. tb and the optimization of detection targets.
Highlights
Mycobacterium tuberculosis (M. tb) isolates with multidrug resistance (MDR) are more difficult to treat than drug-susceptible tuberculosis (TB)
The appearance of multidrug-resistant TB (MDR-TB), including extensively drug-resistant TB (resistance to isoniazid, rifampicin, one fluoroquinolone, and one secondline injectable drug (XDR-TB)) [2], was caused mainly by ineffective treatment, when antibiotics for individual patient are improperly selected or taken, lack of drug-susceptibility testing (DST), and not adopting standard regimens based on the recommendations of the WHO [3,4]
By analyzing the differences in the main missense mutations (MMs) types of the five drugs between the nonextensively drug-resistant (Non-XDR) and preXDR/XDR groups, we found that all MM types of the other four drugs were not significantly different except for streptomycin (Figure 3)
Summary
Mycobacterium tuberculosis (M. tb) isolates with multidrug resistance (MDR) are more difficult to treat than drug-susceptible tuberculosis (TB). The appearance of MDR-TB, including extensively drug-resistant TB (resistance to isoniazid, rifampicin, one fluoroquinolone, and one secondline injectable drug (XDR-TB)) [2], was caused mainly by ineffective treatment, when antibiotics for individual patient are improperly selected or taken, lack of drug-susceptibility testing (DST), and not adopting standard regimens based on the recommendations of the WHO [3,4]. Incorrect diagnosis and treatment of drug-resistant tuberculosis is associated with morbidity, mortality, and ongoing transmission of infection. As one of the countries with the heaviest burden of MDR-TB, China has reported more and more severe drug-resistant isolates in recent years [1,5]. A baseline survey of drug resistance carried out in 2007 showed that the incidence of multidrug resistance in newlytreated tuberculosis patients and retreated patients was 5.7% and 25.6%, respectively [5]
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