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

Abstract

In recent years, the incidence of tuberculosis (TB) and mortality caused by the disease have been decreasing. However, the number of drug-resistant tuberculosis patients is increasing rapidly year by year. Here, a total of 380 Mycobacterium tuberculosis (MTB)-positive formalin-fixed and paraffin-embedded tissue (FFPE) specimens diagnosed in the Department of Pathology of the Eighth Medical Center, Chinese PLA General Hospital were collected. Among 380 cases of MTB, 85 (22.37%) were susceptible to four anti-TB drugs and the remaining 295 (77.63%) were resistant to one or more drugs. The rate of MDR-TB was higher in previously treated cases (52.53%) than in new cases [(36.65%), p < 0.05]. Of previously treated cases, the rate of drug resistance was higher in females than in males (p < 0.05). Among specimens obtained from males, the rate of drug resistance was higher in new cases than in previously treated cases (p < 0.05). Of mutation in drug resistance-related genes, the majority (53/380, 13.95%) of rpoB gene carried the D516V mutation, and 13.42% (51/380) featured mutations in both the katG and inhA genes. Among the total specimens, 18.68% (71/380) carried the 88 M mutation in the rpsL gene, and the embB gene focused on the 306 M2 mutation with a mutation rate of 19.74%. Among the resistant INH, the mutation rate of −15 M was higher in resistance to more than one drug than in monodrug-resistant (p < 0.05). In conclusion, the drug resistance of MTB is still very severe and the timely detection of drug resistance is conducive to the precise treatment of TB.

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

“…In the present study, a higher rate of MDR-TB was detected among previously treated patients than among newly diagnosed TB patients (23.8% vs 4.0%), as well as among patients co-infected with HIV compared to those without HIV (16.7% vs 4.3%). Our findings are supported by previous studies that recognized a higher prevalence of MDR-TB cases among previously treated TB cases than among newly diagnosed TB cases in Addis Ababa, Ethiopia (20.3% vs 5.2%), 30 China (52.53% vs 36.65%) 11 and (34.5% vs 6.8%), 12 and India (12.21% vs 7.81%). 9 In addition to acquired resistance, person-to-person transmission of DR-TB strains is the main mechanism of drug resistance in M. tuberculosis during the course of treatment.…”

“…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.…”

“…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.…”

“…Our results are in line with previous studies conducted in Ethiopia, which also found no isolates with combined mutations in both katG and inhA genes 7 , 31 , 34 or triple mutations at the rpoB , katG , and inhA genes from India. 9 By contrast, other studies have shown a higher rate of double mutations at both the katG and inhA genes of INH-mono-resistant isolates in the Central Africa Republic (4.2%), 36 China (13.4%) 11 and (3.4%), 12 Pakistan (14.7%) 40 and (1.1%), 32 South Africa (22.7%), 41 Burkina Faso (14.5%), 33 and India (3.4%). 9 The extent of INH resistance conferred by various mutations may vary depending on the genetic background of the strain.…”

“…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.…”