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 … Show more
“…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.…”
Section: Discussionsupporting
confidence: 93%
“…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%).…”
Section: Discussionsupporting
confidence: 91%
“…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.…”
Section: Discussionmentioning
confidence: 99%
“…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.…”
Objectives: Molecular approaches to identifying resistance-conferring mutations suggest a revolution in the field of tuberculosis. The aim of the study was to determine the association between resistance-conferring mutations with fitness loss in Mycobacterium tuberculosis clinical isolates and HIV co-infection in the Amhara region of Ethiopia. Methods: A laboratory-based cross-sectional study was conducted between September 2022 and June 2023. A line probe assay was performed on 146 culture-positive clinical isolates. Logistic regression analysis was used to measure the strength of the association between the drug-resistance-conferring mutations with fitness loss in M. tuberculosis isolates and tuberculosis/HIV co-infection. A p-value ⩽ 0.05 was considered statistically significant. Results: A total of 11 distinct mutations at four genetic loci among 19 resistant isolates were detected. The frequency of rifampicin, isoniazid, and fluoroquinolones resistance-conferring mutations was identified in 12 (8.2%), 17 (11.6%), and 2 (1.4%) of the isolates, respectively. The most prominent specific mutations were S450L (5/9, 55.6%), S315T (11/11, 100%), C-15T (4/4, 100%), and D94G (1/1, 100%). Double mutations were observed in 10 (52.6%) multidrug-resistant tuberculosis isolates; the most common were detected in both the rpoB and katG genes (8/10, 80.0%). The HIV-co-infected tuberculosis patients carried a higher proportion of low fitness of non- rpoB S450L variants than those tuberculosis patients without HIV (80.0% vs 14.3%) and showed a significant association (cOR = 0.042, 95% CI: 0.002–0.877, p = 0.041), but not with the low fitness of non- katG S315T variants (cOR = 3.00, 95% CI: 0.348–25.870, p = 0.318). Conclusion: This study provides valuable information on the genetic variants with fitness loss associated with HIV co-infection, but requires further whole-genome-based mutation analysis.
“…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.…”
Section: Discussionsupporting
confidence: 93%
“…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%).…”
Section: Discussionsupporting
confidence: 91%
“…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.…”
Section: Discussionmentioning
confidence: 99%
“…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.…”
Objectives: Molecular approaches to identifying resistance-conferring mutations suggest a revolution in the field of tuberculosis. The aim of the study was to determine the association between resistance-conferring mutations with fitness loss in Mycobacterium tuberculosis clinical isolates and HIV co-infection in the Amhara region of Ethiopia. Methods: A laboratory-based cross-sectional study was conducted between September 2022 and June 2023. A line probe assay was performed on 146 culture-positive clinical isolates. Logistic regression analysis was used to measure the strength of the association between the drug-resistance-conferring mutations with fitness loss in M. tuberculosis isolates and tuberculosis/HIV co-infection. A p-value ⩽ 0.05 was considered statistically significant. Results: A total of 11 distinct mutations at four genetic loci among 19 resistant isolates were detected. The frequency of rifampicin, isoniazid, and fluoroquinolones resistance-conferring mutations was identified in 12 (8.2%), 17 (11.6%), and 2 (1.4%) of the isolates, respectively. The most prominent specific mutations were S450L (5/9, 55.6%), S315T (11/11, 100%), C-15T (4/4, 100%), and D94G (1/1, 100%). Double mutations were observed in 10 (52.6%) multidrug-resistant tuberculosis isolates; the most common were detected in both the rpoB and katG genes (8/10, 80.0%). The HIV-co-infected tuberculosis patients carried a higher proportion of low fitness of non- rpoB S450L variants than those tuberculosis patients without HIV (80.0% vs 14.3%) and showed a significant association (cOR = 0.042, 95% CI: 0.002–0.877, p = 0.041), but not with the low fitness of non- katG S315T variants (cOR = 3.00, 95% CI: 0.348–25.870, p = 0.318). Conclusion: This study provides valuable information on the genetic variants with fitness loss associated with HIV co-infection, but requires further whole-genome-based mutation analysis.
“…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.…”
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.
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