Correlation of inhA mutations and ethionamide susceptibility: Experience from national reference center for tuberculosis

Sarin, Rohit; Bhalla, Manpreet; Kumar, Gyanendra; Singh, Anjali; Myneedu, Vithal Prasad; Singhal, Ritu

doi:10.4103/lungindia.lungindia_120_21

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…This suggests that mutation of the inhA gene does not always indicate a low resistance level. Due to the common target of action, mutations in the inhA gene also confer cross-resistance to ethionamide (ETH), a second-line drug used in MDR therapy, and thus considered as a surrogate marker for early detection of ETH resistance [8,39,40]. Previously, the National Department of Health (NDoH) in South Africa included ETH in the treatment regimen for MDR-TB in South Africa.…”

Section: Discussionmentioning

confidence: 99%

“…According to van Soolingen et al [52] Beijing lineage was described for the first time in East Asian countries with a specific spoligotype pattern characterized by the presence of the last 10 spacers (spacers [34][35][36][37][38][39][40][41][42][43]. Historical evidence supported by genetic data established that the Beijing strains were historically recently brought to South Africa, not directly from its primary origin (China), but from the secondary one (Indonesia) [46].…”

Section: Discussionmentioning

confidence: 99%

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

Faye¹,

Hosu²,

Sineke³

et al. 2023

Preprint

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Drug-resistant tuberculosis (DR-TB) remains a major public health problem in South Africa. Gene mu-tations and the genotyping of DR-TB in a rural Eastern Cape Province have not previously been studied. Hence, we sought to detect prevalent mutations linked to DR-TB profiles, identify genetic diversity, and assign lineages. Sputum specimens were obtained from 1157 patients suspected with tuberculosis. They were assayed for rifampin-resistance using Xpert® MTB/RIF.and detection of mutations conferring re-sistance to anti-TB drugs was carried out using GenoType MTBDRplus VER 2.0. Thereafter, 441 isolates were spoligotyped. The most prevalent rifampin resistance-conferring mutations were in rpoB codon S531L. The INH resistant strains, 54.5% had mutations in katG gene at codon S315TB and 24.7% with mutations in inhA gene at codons C-15TB. Furthermore 69.9% strains displayed mutations involving both rpoB and katG genes, while 24.6% strains displayed mutations involving both rpoB and inhA genes. The overall prevalence of heteroresistance was 17.9%. Spoligotyping analysis generated 410 patterns of iso-lates which were found in the international database, with Beijing family being predominant. The diversity of mutations in the study provides information for investigating the evolutional lineages of M. tuberculosis isolates. The recognition frequency of rpoB, katG and inhA mutations in different study areas may help to guide decision‑making about standardization of treatment regimens or individualized treatment in areas where these mutations have been found. This calls for increased drug resistance surveillance and rein-forcement of TB control in this area.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Faye¹,

Hosu²,

Sineke³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This suggests that mutation of the inhA gene does not always indicate a low resistance level. Mutations in the inhA gene also give rise to cross-resistance to ethionamide (ETH), a second-line medication used in MDR therapy, and are therefore thought of as a surrogate marker for early diagnosis of ETH resistance [ 10 , 47 , 48 ]. This is because the two drugs share the same target of action.…”

Section: Discussionmentioning

confidence: 99%

The Detection of Mutations and Genotyping of Drug-Resistant Mycobacterium tuberculosis Strains Isolated from Patients in the Rural Eastern Cape Province

Faye

Hosu

Oostvogels

et al. 2023

Infectious Disease Reports

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Drug-resistant tuberculosis (DR-TB) is still a major public health concern in South Africa. Mutations in M. tuberculosis can cause varying levels of phenotypic resistance to anti-TB medications. There have been no prior studies on gene mutations and the genotyping of DR-TB in the rural Eastern Cape Province; hence, we aimed to identify DR-TB mutations, genetic diversity, and allocated lineages among patients in this area. Using Xpert® MTB/RIF, we assessed the rifampin resistance of sputum samples collected from 1157 patients suspected of having tuberculosis. GenoType MTBDR plus VER 2.0 was used for the detection of mutations causing resistance to anti-TB medications. The next step was to spoligotype 441 isolates. The most prevalent rifampin resistance-conferring mutations were in rpoB codon S531L in INH-resistant strains; the katG gene at codon S315TB and the inhA gene at codon C-15TB had the most mutations; 54.5% and 24.7%, respectively. In addition, 24.6% of strains showed mutations in both the rpoB and inhA genes, while 69.9% of strains showed mutations in both the katG and rpoB genes. Heteroresistance was seen in 17.9% of all cases in the study. According to spoligotyping analysis, Beijing families predominated. Investigation of the evolutionary lineages of M. tuberculosis isolates can be carried out using the information provided by the study’s diversity of mutations. In locations wherein these mutations have been discovered, decision-making regarding the standardization of treatment regimens or individualized treatment may be aided by the detection frequency of rpoB, katG, and inhA mutations in various study areas.

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Resistance and tolerance of Mycobacterium tuberculosis to antimicrobial agents—How M. tuberculosis can escape antibiotics

Yuan

Duan

2022

WIREs Mechanisms of Disease

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Tuberculosis (TB) poses a serious threat to public health worldwide since it was discovered. Until now, TB has been one of the top 10 causes of death from a single infectious disease globally. The treatment of active TB cases majorly relies on various anti-tuberculosis drugs. However, under the selection pressure by drugs, the continuous evolution of Mycobacterium tuberculosis (Mtb) facilitates the emergence of drug-resistant strains, further resulting in the accumulation of tubercle bacilli with multiple drug resistance, especially deadly multidrug-resistant TB and extensively drug-resistant TB. Researches on the mechanism of drug action and drug resistance of Mtb provide a new scheme for clinical management of TB patients, and prevention of drug resistance. In this review, we summarized the molecular mechanisms of drug resistance of existing anti-TB drugs to better understand the evolution of drug resistance of Mtb, which will provide more effective strategies against drug-resistant TB, and accelerate the achievement of the EndTB Strategy by 2035.

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Correlation of inhA mutations and ethionamide susceptibility: Experience from national reference center for tuberculosis

Cited by 5 publications

References 14 publications

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

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

The Detection of Mutations and Genotyping of Drug-Resistant Mycobacterium tuberculosis Strains Isolated from Patients in the Rural Eastern Cape Province

Resistance and tolerance of Mycobacterium tuberculosis to antimicrobial agents—How M. tuberculosis can escape antibiotics

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