Frequency of mutations associated with isoniazid-resistant in clinical Mycobacterium tuberculosis strains by low-cost and density (LCD) DNA microarrays

Sadri, Hadis; Farahani, Abbas; Mohajeri, Parviz

doi:10.4103/1755-6783.190166

Cited by 10 publications

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“…32 The KatG S315T1 substitution (100%) was the most frequent specific variant that caused high-level INH resistance in our study. This finding aligns with the previous studies that identified the S315T1 variant as the most common genetic variation in the katG gene in Northwest Ethiopia (70.6%) 6 and (87.8%), 7 Addis Ababa Ethiopia (76.9%), 5 Iran (70%), 35 India (86.3%), 9 China (73.8%), 37 Burkina Faso (77.3%), 33 and Pakistan (78.2%) 32 ; but higher S315T1 mutation reported in Eastern Ethiopia (91.8%), 34 Addis Ababa Ethiopia (100%), 30 India (96.2%), 13 central Africa Republic (94.2%), 36 and Mongolia (99.1%) 42 ; and lower proportions of S315T1specific mutations were observed in Northeastern Ethiopia (25%), 4 China (62.9%), 12 Iran (32%), 43 and Pakistan (69.8%). 2 A specific C-15T mutation in the inhA regulatory region was detected in a higher proportion of 100% in our study, which is consistent with previously reported results in Eastern Ethiopia (100), 34 Mongolia (98.0%), 42 and India (88.9%) 9 ; however, lower rates were detected in Northwest Ethiopia (41%) 6 and (3.3%), 7 Addis Ababa Ethiopia (30.8%), 5 Tigray region of Ethiopia (5%), 31 China (5.7%) 12 and (24.6%), 37 South Africa (13.4%), 41 and Pakistan (14.9%) 32 and (5.6%).…”

Section: Discussionmentioning

confidence: 96%

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

Seid,

Kassa,

Girma

et al. 2023

SAGE Open Medicine

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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.

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Section: Discussionmentioning

confidence: 96%

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

Seid,

Kassa,

Girma

et al. 2023

SAGE Open Medicine

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“…For INH, the katG gene has such mutations. The most common is at codon 315 (S > T) and is found in 50–95% of INH-resistant clinical isolates [ 5 ], and in 82.95% [ 6 ], 56% [ 7 ], and 32% [ 8 , 9 ] of INH-resistant strains. The katG gene mutation at codon 315 (changed amino acid serine to threonine (AGC > ACC)) was found in 60% of isoniazid-resistant isolates using PCR-RFLP [ 10 ] and 94% of MDR-TB samples using sequencing [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Heteroresistance of Mycobacterium tuberculosis in the Sputum Detected by Droplet Digital PCR

Aung

Faksri

Sangka

et al. 2023

Biology

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Heteroresistance in MTB refers to the presence of distinct subpopulations of bacteria with varying levels of antibiotic susceptibility within a population. Multidrug-resistant and rifampicin-resistant TB are serious global health concerns. In this study, we aimed to determine the prevalence of heteroresistance in MTB from sputum samples of new TB cases using Droplet Digital PCR mutation detection assays for katG and rpoB genes, which are commonly associated with resistance to isoniazid and rifampicin, respectively. We found that out of 79 samples, 9 (11.4%) exhibited mutations in katG and rpoB genes. INH mono-resistant TB, RIF mono-resistant TB, and MDR-TB samples constituted 1.3%, 6.3%, and 3.8% of new TB cases, respectively. Heteroresistance in katG, rpoB, and both genes were found in 2.5%, 5%, and 2.5% of total cases, respectively. Our results suggest that these mutations may have arisen spontaneously, as the patients had not yet received anti-TB drugs. ddPCR is a valuable tool for the early detection and management of DR-TB, as it can detect both mutant and wild-type strains in a population, enabling the detection of heteroresistance and MDR-TB. Overall, our findings highlight the importance of early detection and management of DR-TB for effective TB control (in katG, rpoB, and katG/rpoB).

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The pncA gene mutations of Mycobacterium tuberculosis in multidrug‐resistant tuberculosis

Mahmood

Bhatti

Abbas

et al. 2021

Biotech and App Biochem

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The pncA gene encodes pyrazinamidase enzyme which converts drug pyrazinamide to active form pyrazinoic acid, but mutations in this gene can prevent enzyme activity which leads to pyrazinamide resistance. The cross‐sectional study was carried out during 2016–2017 for 12 months. The purpose of the study was to detect mutation at codon 12 and codon 85 in the pncA gene in local multidrug‐resistant tuberculosis (MDR‐TB) patients by developing a simple molecular test so that disease could be detected timely in the local population. DNA extracted from sputum‐cultured samples from MDR‐TB patients and subjected to semi‐multiplex allele‐specific PCR by using self‐designed primers against the pncA gene. Among 75 samples, 53 samples were subjected to molecular analysis based on purified DNA quantity and quality. The primers produced 250 and 480 bp fragments, indicating the mutations at codon 12 (aspartate to alanine) and codon 85 (leucine to proline) respectively. MDR‐TB was more common in the age group 21–40 years. Fifty‐seven percent of samples (n = 30) were found positive for pncA mutations, whereas 43% of samples (n = 23) showed negative results. Thirteen percent of samples (n = 4) had mutations at codon 12 in which aspartate was converted to alanine, and they produced an amplified product of 480 bp. Eighty‐seven percent of samples (n = 26) had mutations at codon 85 in which leucine was converted to proline and amplified product size was 250 bp. The mutations were simple nucleotide substitutions. The prevalence of mutations in which leucine was substituted by proline was higher than the mutations in which aspartate was substituted by alanine. A high prevalence of substitution mutation (CTG → CCG; leucine to proline) was detected in MDR‐TB cases. Earlier detection of MDR‐TB via an effective molecular diagnostic method can control the MDR tuberculosis spread in the population.

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Frequency of mutations associated with isoniazid-resistant in clinical Mycobacterium tuberculosis strains by low-cost and density (LCD) DNA microarrays

Cited by 10 publications

References 0 publications

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

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

Heteroresistance of Mycobacterium tuberculosis in the Sputum Detected by Droplet Digital PCR

The pncA gene mutations of Mycobacterium tuberculosis in multidrug‐resistant tuberculosis

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