Analysis on Drug-Resistance-Associated Mutations among Multidrug-Resistant Mycobacterium tuberculosis Isolates in China

Abstract

As the causative bacteria of tuberculosis, Mycobacteriumtuberculosis (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.

Detection of Mutations and Genotyping of Drug-Resistant Mycobacterium Tuberculosis Strains Isolated From Patients in Rural Eastern Cape Province

“…Conversely, the studies of [9,20,21] reported a prevalent mutation of 93.5%, 94.9%, and 91.2% respectively in katG gene which is higher than what was obtained in this study. In this study, the most prevalent rifampin resistance-conferring mutations in rpoB occurred in S531L codon which is comparable with previous studies [9,20,22,23], and could be due to the spread of a prevalent clone. Mutation in this codon is identified as a hot spot for rpoB gene mutations in M. tuberculosis and has been reported in other Provinces of South Africa as well [24] showing that these mutations are prevalent in the country.…”

“…This is comparable to the study done by Otchere et al, with a prevalence of 52% [19]. Conversely, the studies of [9,20,21] reported a prevalent mutation of 93.5%, 94.9%, and 91.2% respectively in katG gene which is higher than what was obtained in this study. In this study, the most prevalent rifampin resistance-conferring mutations in rpoB occurred in S531L codon which is comparable with previous studies [9,20,22,23], and could be due to the spread of a prevalent clone.…”

“…[23]. Low frequency of mutation was observed in codon 526 at 3.8% in this study but higher in Uganda at 12.5% [25]; China at 14.9% [20]; Brazil at 9.9%, [26] indicating that frequency varies with different geographic locations. The co-occurrence rate of codons 526D and 531 in this study (2.8%) was lower than the rate reported in Iran (23.9%) [27].…”

Epidemiological characteristics and risk factors of multidrug-resistant tuberculosis in Luoyang, China

“…Although resistance to rifampicin and isoniazid is significantly associated with mutations in the Mycobacterium tuberculosis resistance genes rpoB, katG, inhA , and ahpC , these mutations vary in location and frequency in different regions ( 27 , 28 ). For example, the mutation rate at rpoB 531 is as high as 80.9% in Kazakhstan and only 31% in Hungary, and the two mutation patterns of katG 315 and inhA account for a total of 79.9% in Beijing, China ( 27 ).…”

An overview of the pattern of first- and second-line anti-tuberculosis drug resistance gene mutations

“…INH is the most widely used anti-TB medicine, and INH resistance is more widespread among clinical strains than susceptibility to any other agent [21]. In INH-resistant clinical isolates, mutations in the M. tuberculosis gene are most prevalent, occurring in 50-80% of infections, limiting the catalase-ability peroxidase to trigger the INH pro-drug [22].…”