Molecular identification of mutations conferring resistance to rifampin, isoniazid and pyrazinamide among<i>Mycobacterium tuberculosis</i>isolates from Iran

Haratiasl, Ahad Ali; Hamzelou, Gholamreza; Amini, Sirus; Kardan-Yamchi, Jalil; Haeili, Mehri; Heidari, Fereshteh; Feizabadi, Mohammad Mehdi

doi:10.1080/1120009x.2020.1716479

Cited by 10 publications

(4 citation statements)

References 23 publications

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“…Our results showed that 50 of the 56 INH-resistant isolates had S315T mutations, and 8 isolates with mutations in the inhA promoter sequence were found. Furthermore, increasing reports indicate that RFP-resistant M. tuberculosis strains are often resistant to INH as well [35][36][37], which is consistent with the results of the present study. Our study revealed that 82.8% of RFP resistant isolates (53/64) were simultaneously resistant to INH.…”

Section: Discussionsupporting

confidence: 93%

Establishment and evaluation of an overlap extension polymerase chain reaction technique for rapid and efficient detection of drug-resistance in Mycobacterium tuberculosis

Ouyang

Yuan

et al. 2022

Infect Dis Poverty

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Background Rapid and accurate detection of drug resistance in Mycobacterium tuberculosis is critical for effective control of tuberculosis (TB). Herein, we established a novel, low cost strategy having high accuracy and speed for the detection of M. tuberculosis drug resistance, using gene splicing by overlap extension PCR (SOE PCR). Methods The SOE PCR assay and Sanger sequencing are designed and constructed to detect mutations of rpoB, embB, katG, and inhA promoter, which have been considered as the major contributors to rifampicin (RFP), isoniazid (INH), and ethambutol (EMB) resistance in M. tuberculosis. One hundred and eight M. tuberculosis isolates came from mycobacterial cultures of TB cases at Chongqing Public Health Medical Center in China from December 2018 to April 2019, of which 56 isolates were tested with the GeneXpert MTB/RIF assay. Performance evaluation of the SOE PCR technique was compared with traditional mycobacterial culture and drug susceptibility testing (DST) or GeneXpert MTB/RIF among these isolates. Kappa identity test was used to analyze the consistency of the different diagnostic methods. Results We found that the mutations of S531L, S315T and M306V were most prevalent for RFP, INH and EMB resistance, respectively, in the 108 M. tuberculosis isolates. Compared with phenotypic DST, the sensitivity and specificity of the SOE PCR assay for resistance detection were 100.00% and 88.00% for RFP, 94.64% and 94.23% for INH, and 68.97% and 79.75% for EMB, respectively. Compared with the GeneXpert MTB/RIF, the SOE PCR method was completely consistent with results of the GeneXpert MTB/RIF, with a concordance of 100% for resistance to RFP. Conclusions In present study, a novel SOE PCR diagnostic method was successfully developed for the accurate detection of M. tuberculosis drug resistance. Our results using this method have a high consistency with that of traditional phenotypic DST or GeneXpert MTB/RIF, and SOE PCR testing in clinical isolates can also be conducted rapidly and simultaneously for detection of drug resistance to RFP, EMB, and INH. Graphical Abstract

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Section: Discussionsupporting

confidence: 93%

Establishment and evaluation of an overlap extension polymerase chain reaction technique for rapid and efficient detection of drug-resistance in Mycobacterium tuberculosis

Ouyang

Yuan

et al. 2022

Infect Dis Poverty

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“…Vaziri et al (28) in 2019 revealed that MDR-TB strains have several mutations that cause primary resistance to various antituberculosis drugs. We also found that the frequency of resistance to pyrazinamide was significantly higher than that of mono-resistance in TB strains that confirm previous Iranian reports (25,29).…”

Section: Changes In Nucleotide Amino Acid Changessupporting

confidence: 91%

“…In a recent eight-year prospective study on Iranian TB cases, the average prevalence of MDR-TB cases was reported as 14.18% that was significantly higher than the global average (3.5%) (24). Haratiasl et al (25) in 2020 showed that the prevalence of pyrazinamide resistance is high among Iranian MDR-TB patients. Several studies have suggested that the frequency of the Beijing family in MDR-TB strains is significantly more than that of other lineages (26,27).…”

Section: Changes In Nucleotide Amino Acid Changesmentioning

confidence: 99%

Evaluating the Frequency of Resistance to Pyrazinamide Among Drug-resistant Strains of Mycobacterium tuberculosis in Isfahan, Iran

Nasr-Esfahani

Moghim

Salehi³

et al. 2021

Arch Clin Infect Dis

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Background: Pyrazinamide is one of the most important first-line medications for the treatment of tuberculosis and an alternative intake for MDR-TB and XDR-TB patients. Objectives: The purpose of this study was to evaluate resistance to pyrazinamide in the isolates resistant to the Mycobacterium tuberculosis drug in patients in the city of Isfahan. Methods: In this study, the drug susceptibility test was performed with pyrazinamide using the proportion method and PZA assay on 47 isolates resistant to Mycobacterium tuberculosis. Then, the mutations of the pncA and rpsA genes of the isolates resistant to pyrazinamide were evaluated by the sequencing method. Results: According to the proportion method, 19 cases were resistant to pyrazinamide, 16 of which had mutations in their pncA and rpsA genes. Besides, five new mutations were recorded, and three isolates lacked mutations in the mentioned genes. Conclusions: Pyrazinamide resistance is high in MDR-TB and INH mono-resistant isolates. Therefore, evaluating the susceptibility to pyrazinamide in patients with MDR-TB before the initiation of treatment with pyrazinamide is considered essential.

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“…Speci cally, PZA plays a role in combating the deteriorating effects of TB, shortening the course of its treatment and the treatment of patients infected with isoniazid-and rifampicin-resistant strains [25]. However, several studies indicate that Mtb strains resistant to isoniazid are also resistant to PZA due to mutations in the target genes [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Towards the development of better therapeutic agents for Mycobacterium Tuberculosis: Computational design and evaluation of pyrazinone derivatives as inhibitors of enoyl acyl carrier protein reductase

Goel,

Negi,

Aggarwal

et al. 2024

Preprint

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The treatment of tuberculosis (TB) has become challenging due to the emergence of multidrug-resistant strains of Mycobacterium tuberculosis. Consequently, new, and efficient therapies need to be developed to combat this dreaded disease. In this study, we apply in-silico techniques to analyse the potential inhibitory role of pyrazinone derivatives for enoyl-acyl carrier protein reductase (InhA), an important component protein involved in the synthesis of mycolic acids, the major components of the mycobacterial cell wall. Specifically, we amalgamated molecular docking, molecular dynamics (MD) simulations and quantum mechanical (QM) calculations to analyse the interaction of InhA with eight distinct pyrazinone derivatives, that contain thiophenyl, phenyl, or chloro substitutions at C6, ethyl or methoxybenzyl substitutions at N4, and carboxylate group (hydrolysed form of the parent carbonitrile group) at C2 position of the pyrazinone skeleton and compared our results with isoniazid, a well-known first-line TB drug that potentially inhibits InhA. Docking suggests that despite binding within the same pocket (albeit with different residues), pyrazinone derivatives interact more strongly with InhA than isoniazid. This points towards the potentially greater efficacy of these compounds than isoniazid towards InhA inhibition. Further, although C6 substitution does not significantly affect the ligand binding, N4-methoxybenzyl derivatives exhibit higher docking scores than their N4-ethyl counterparts, thereby suggesting their promising inhibitory potential against InhA. Extended (500 ns) all-atom explicit solvent MD simulations, amounting to a total of 9 µs of the simulation time, provide a refined picture of ligand binding in the explicit-solvent environment, and suggest that the crucial interaction with Arg 194 observed in the docked structures is mostly retained. Analysis of the hydrogen bond occupancies and binding-site linear interaction energies reiterate that the binding of the pyrazinone derivatives with InhA is stronger than isoniazid. In synchrony with MMGBSA binding energy calculations and QM calculations, these analyses reveal that irrespective of the nature of C6 substitution, pyrazinone derivatives with N4-methoxybenzyl substitution exhibit stronger binding to InhA, compared to those containing N4-ethyl substitution. Overall, this study identifies promising candidate compounds that should be experimentally tested for their potential inhibitory effects towards InhA.

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Molecular identification of mutations conferring resistance to rifampin, isoniazid and pyrazinamide amongMycobacterium tuberculosisisolates from Iran

Cited by 10 publications

References 23 publications

Establishment and evaluation of an overlap extension polymerase chain reaction technique for rapid and efficient detection of drug-resistance in Mycobacterium tuberculosis

Establishment and evaluation of an overlap extension polymerase chain reaction technique for rapid and efficient detection of drug-resistance in Mycobacterium tuberculosis

Evaluating the Frequency of Resistance to Pyrazinamide Among Drug-resistant Strains of Mycobacterium tuberculosis in Isfahan, Iran

Towards the development of better therapeutic agents for Mycobacterium Tuberculosis: Computational design and evaluation of pyrazinone derivatives as inhibitors of enoyl acyl carrier protein reductase

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