Drug Resistance Pattern of Mycobacterium tuberculosis Isolates From Patients Referred to TB Reference Laboratory in Ahvaz

Badie, Fereshteh; Arshadi, Maniya; Mohsenpoor, Maryam; Gharibvand, Soodabeh S.

doi:10.1016/j.phrp.2015.10.010

Cited by 5 publications

(6 citation statements)

References 11 publications

(11 reference statements)

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“…As mentioned earlier, the existence of extended borders with countries where TB is endemic and immigrations of these populations influenced TB distribution in the region and threatens the control strategies. In some provinces such as Khuzestan we found some similar MIRU types of 10 and 16 with neighbor country of Iraq, although the MDR rate was much higher in Iraq compared to the rate demonstrated in Khuzestan by other investigators as 3.1% [37]. The MDR rate in Sistan‐Baluchestan was close to Pakistan in the same region, while the MIRU types were different.…”

Section: Discussionsupporting

confidence: 48%

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Genetic diversity of multidrug‐resistant Mycobacterium tuberculosis strains isolated from tuberculosis patients in Iran using MIRU‐VNTR technique

Khosravi

Shahraki

Dezfuli

et al. 2017

The Kaohsiung J of Med Scie

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Tuberculosis (TB) is considered as one of the most important infectious diseases in the world, and recent rise and spread of multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains, have made the matter worsened. Due to the importance of TB prevalence in Iran, this study was designed to investigate the genetic diversity among MDR strains of MTB by MIRU-VNTR typing scheme. A total of 88 drug resistant M. tuberculosis isolates belong to pulmonary TB cases were collected from several TB reference centers of Iran. Drug susceptibility testing for Isoniazid and Rifampin was performed using the agar proportion method and MDR isolates were underwent genotyping by using 12-locus- based MIRU-VNTR typing. On performing proportion method, 22 isolates were identified as MDR. By typing of MDR isolates using 12-loci MIRU-VNTR technique, high diversity were demonstrated in MDR strains and these were classified into 20 distinct MIRU-VNTR genotypes. MIRU loci 10 and 26 were the most discriminatory loci with 8 and 7 alleles respectively; while MIRU loci 2, 20, 24 and 39 were found to be the least discriminatory with 1-2 alleles each. We noticed a mixed infection in isolate 53, as this isolate comprised simultaneous two alleles in MIRU loci 40, 10, 16 and 39. In conclusion, this result represents MIRU-VNTR typing as a useful tool for studying genetic diversity of MDR-MTB in regional settings, and will help the health sectors to construct a preventive program for MDR-TB. Additionally, it can detect mixed infection which can facilitate management of treatment.

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Section: Discussionsupporting

confidence: 48%

“…In all mentioned studies, the discriminatory index for MIRU-VNTR was high from 0.991 in present study to 0.999 in study of Zheng et al [10], and this shows the successful application of the technique for screening the MTB isolates. (4,6,14,15,33,37,47,48,53,57,65,66); note to lane 9, representing isolate no. 53 with 2 alleles of 4 and 5.…”

Section: Discussionmentioning

confidence: 99%

Genetic diversity of multidrug‐resistant Mycobacterium tuberculosis strains isolated from tuberculosis patients in Iran using MIRU‐VNTR technique

Khosravi

Shahraki

Dezfuli

et al. 2017

The Kaohsiung J of Med Scie

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“…Tuberculosis remains the leading cause of death worldwide with the frequency of mutations in rifampicin and isoniazid resistance varying according to geographical location [ 1 ]. Tuberculosis (TB) is caused by Mycobacterium tuberculosis; a slow growing bacterium, which requires 4-8 weeks to isolate, identify and confirm drug susceptibility tests [ 2 – 4 ].…”

Section: Introductionmentioning

confidence: 99%

Mutations in rpoB and katG genes of multidrug resistant mycobacterium tuberculosis undetectable using genotyping diagnostic methods

Takawira¹,

Mandishora²,

Dhlamini³

et al. 2017

Pan Afr Med J

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IntroductionTuberculosis remains the leading causes of death worldwide with frequencies of mutations in rifampicin and isoniazid resistant Mycobacterium tuberculosis isolates varying according to geographical location. There is limited information in Zimbabwe on specific antibiotic resistance gene mutation patterns in MTB and hence, increased rate of discordant results and mortality due to inappropriate antibiotic prescriptions. The rpoB and katG genes molecular markers are used for detecting rifampicin and isoniazid resistance respectively. Some mutations within these gene sequences are associated with drug resistance as they directly alter gene function. The objectives of this research was to determine the drug resistance profiles in M. tuberculosis isolates that are phenotypically resistant but not detected by the GeneXpert and MTBDRplus kit and also to detect mutations in the rpoB and katG genes which are not detected by the Hain Genotype MTBDRplus kit and GeneXpert diagnosis.MethodsPCR was used for the amplification of the rpoB and katG genes from MTB isolates collected from human clinical samples between 2008 and 2015. The genes were sequenced and compared to the wild type MTB H37Rv rpoB (accession number L27989) and kat G genes (KP46920), respectively. Sequence analysis results were compared to genotyping results obtained from molecular assays and culture results of all isolates.ResultsThe most frequent mutation responsible for rifampicin resistance was (25/92) S531L that was detected by using all molecular assays. Some inconsistencies were observed between phenotypic and genotypic assay results for both katG and rpoB genes in 30 strains. For these, eight codons; G507S, T508A, L511V, del513-526, P520P, L524L, R528H, R529Q and S531F were novel mutations. In addition, the I572P/F, E562Q, P564S, and Q490Y mutations were identified as novel mutations outside the rifampicin resistance determining region. In katG gene, amino acid changes to threonine, asparagine and isoleucine exhibited high degrees of polymorphism such as V473N, D311N, and L427I. The R463L (20/92) amino acid substitution was most common but was not associated with isoniazid resistance.ConclusionThese finding indicate that molecular assay kit diagnosis that is based on the rpoB and katG genes should be improved to cater for the genetic variations associated with the geographic specificity of the target genes and be able to detect most prevalent mutations in different areas.

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“…Tuberculosis (TB) remains a major public health problem globally, with resistance to rifampicin (RIF) and isoniazid (INH), the main anti-TB first-line drugs, varying according to geographical location [ 1 , 2 ]. The number of TB patients diagnosed and treated for multidrug-resistant tuberculosis (MDR-TB) is increasing worldwide, and treatment success rates in patients with drug-resistant TB remain unacceptably low [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

The Structural Basis of Mycobacterium tuberculosis RpoB Drug-Resistant Clinical Mutations on Rifampicin Drug Binding

2022

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Tuberculosis (TB), caused by the Mycobacterium tuberculosis infection, continues to be a leading cause of morbidity and mortality in developing countries. Resistance to the first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF), is a major drawback to effective TB treatment. Genetic mutations in the β-subunit of the DNA-directed RNA polymerase (rpoB) are reported to be a major reason of RIF resistance. However, the structural basis and mechanisms of these resistant mutations are insufficiently understood. In the present study, thirty drug-resistant mutants of rpoB were initially modeled and screened against RIF via a comparative molecular docking analysis with the wild-type (WT) model. These analyses prioritized six mutants (Asp441Val, Ser456Trp, Ser456Gln, Arg454Gln, His451Gly, and His451Pro) that showed adverse binding affinities, molecular interactions, and RIF binding hinderance properties, with respect to the WT. These mutant models were subsequently analyzed by molecular dynamics (MD) simulations. One-hundred nanosecond all-atom MD simulations, binding free energy calculations, and a dynamic residue network analysis (DRN) were employed to exhaustively assess the impact of mutations on RIF binding dynamics. Considering the global structural motions and protein–ligand binding affinities, the Asp441Val, Ser456Gln, and His454Pro mutations generally yielded detrimental effects on RIF binding. Locally, we found that the electrostatic contributions to binding, particularly by Arg454 and Glu487, might be adjusted to counteract resistance. The DRN analysis revealed that all mutations mostly distorted the communication values of the critical hubs and may, therefore, confer conformational changes in rpoB to perturb RIF binding. In principle, the approach combined fundamental molecular modeling tools for robust “global” and “local” level analyses of structural dynamics, making it well suited for investigating other similar drug resistance cases.

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Drug Resistance Pattern of Mycobacterium tuberculosis Isolates From Patients Referred to TB Reference Laboratory in Ahvaz

Cited by 5 publications

References 11 publications

Genetic diversity of multidrug‐resistant Mycobacterium tuberculosis strains isolated from tuberculosis patients in Iran using MIRU‐VNTR technique

Genetic diversity of multidrug‐resistant Mycobacterium tuberculosis strains isolated from tuberculosis patients in Iran using MIRU‐VNTR technique

Mutations in rpoB and katG genes of multidrug resistant mycobacterium tuberculosis undetectable using genotyping diagnostic methods

The Structural Basis of Mycobacterium tuberculosis RpoB Drug-Resistant Clinical Mutations on Rifampicin Drug Binding

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