Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

Abstract

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

Molecular characterization of genetic mutations with fitness loss in pulmonary tuberculosis patients associated with HIV co-infection in Northwest Amhara, Ethiopia

“…2 The reasons for differences in the frequency of genetic mutations might be due to variations in the sample size, the methodology used to characterize mutations, and sociodemographic factors such as prior TB treatment and HIV co-infection, which is supported by Ranjan et al 13 A total of 16.7% of INH-resistant isolates showed unknown mutations in the katG gene. Our finding is consistent with previously defined reports of uncertain katG mutations in the Tigray region of Ethiopia (17.1%), 31 China (20%), 12 Burkina Faso (3.6% katG), 33 and India (13%). 9 It is known that approximately 10%-25% of INH-resistant strains with uncertain mutations have mutations outside of the KatG and inhA genetic loci.…”

“…The most common genetic variant in the rpoB gene associated with high levels of resistance to RIF was found to be at codon S450L (55.6%), followed by H445Y and D435V (22.2%). Our findings in S450L are consistent with the high rates reported in other studies across various regions such as Eastern Ethiopia (59.1%), 34 Northwest Ethiopia (64.0%), 7 Iran (66%), 35 the Central Africa Republic (53.4%), 36 Pakistan (55.6%) 32 and (64.1%), 2 India (58.8%), 9 and China (62.5%) 12 and (58.2%). 37 By contrast, the frequency of mutation at codon S450L in our study was higher than the previous report from Iran (40%) 38 and China (31.25%) 39 but lower than studies conducted in the Tigray region of Ethiopia (70%), 31 Addis Ababa Ethiopia (81.3%), 30 and Pakistan (85%).…”

“…The possible reasons for the differences in the occurrence of specific mutations in the rpoB gene could be due to the patterns of drug resistance-conferring mutations, geographic locations, and sociodemographic characteristics of the study participants, including HIV co-infection and prior TB therapy. This assumption is supported by the research of Welekidan et al 31 Out of the 17 INH-resistant isolates, a total of 64.7% had specific mutations at codon 315 of the katG gene, which is similar to the previously reported findings in Northwest Ethiopia (70.6%), 6 Northeastern Ethiopia (66.7%), 4 India (71.9%), 13 China (57.6%), 11 and South Africa (63.9%), 41 but lower than from Northwest Ethiopia (87.8%), 7 the Tigray region of Ethiopia (78%), 31 Eastern Ethiopia (96.5%), 34 India (75.3%), 9 China (85.4%), 12 and Pakistan (81.6%). 32 The KatG S315T1 substitution (100%) was the most frequent specific variant that caused high-level INH resistance in our study.…”

“…9 Resistance to anti-TB drugs in M. tuberculosis isolates is obtained mainly through mutations in drug resistance-related genes, such as rpoB gene encoding the β subunit of RNA polymerase in the 81-bp hotspot region of the rifampicin (RIF) resistance determining region (RRDR) 10 ; responsible for resistance; katG, inhA, and fabG promoters that confer isoniazid (INH) resistance; gyrA and gyrB genes linked to fluoroquinolones (FQs) resistance; rrs, eis, and tlyA genes are responsible for the injectable agent (IA) resistance. 11,12 The accumulation of point mutations in coding regions for drug targets and/or drug-converting enzymes is a major mechanism for acquiring resistance by reducing the bacterium's susceptibility to drugs 13 because the tubercle bacilli have no known efficient mechanism for horizontal gene transfer. 14 When bacteria develop drug-resistant mutations, there is often an associated biological cost of M. tuberculosis isolates.…”

Drug Resistance and Molecular Characteristics of Mycobacterium tuberculosis: A Single Center Experience

“…While eliminating pathogenic MTB, they also select drug-resistant bacteria against which the drugs are useless [9]. Resistance to anti-MTB drugs is obtained mainly through mutations in distinctive drug resistance-related genes [10,11], which mainly include rpoB, inhA, katG, rpsL, and embB [11]. The molecular mechanisms by which MTB develops resistance to each drug are different.…”