Contribution of AGC to ACC and other mutations at codon 315 of the katG gene in isoniazid-resistant Mycobacterium tuberculosis isolates from the Middle East

Ahmad, Suhail; Mokaddas, Eiman

doi:10.1016/j.ijantimicag.2003.10.004

Cited by 36 publications

(23 citation statements)

References 22 publications

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“…Among these, the katG gene was the most frequently mutated (80.8%; 181/224). The mutation in codon 315 of the katG gene was present in 178 isolates, comparable to the previously reported rate for patients diagnosed in Kuwait, Brazil and The Netherlands (65% and 55%, respectively), but lower than described in Russia [32,[50][51][52]. Mutations in inhA regulatory region were the second most frequent (9.8%), following by ahpC gene (8.9%), and inhA ORF region (1.3%).…”

Section: Isoniazid (Inh)supporting

confidence: 78%

Review: The Molecular Basis of Resistance in <i>Mycobaterium tuberculosis</i>

Santos¹

2012

OJMM

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Tuberculosis is a serious global public health problem and its high prevalence is strongly associated with the increase of drug resistance. This steady increase in the frequency of M. tuberculosis strains resistant to one or more agents commonly used to treat tuberculosis has drawn worldwide attention to understanding the molecular basis of resistance in M. tuberculosis. TB resistance is a great concern in the antibiotic resistance pandemic due to the high risk of death, as patients can remain infected for months or years and also because of the difficulty of the treatment. A molecular understanding of the series of events that render M. tuberculosis multi-drug resistant is very important in order to find a fast and appropriated diagnosis as well as a new target for new drugs.

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Section: Isoniazid (Inh)supporting

confidence: 78%

Review: The Molecular Basis of Resistance in <i>Mycobaterium tuberculosis</i>

Santos¹

2012

OJMM

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“…Mutations affecting this codon are responsible for INH resistance in ca. 60% of the cases worldwide (1,20). The simultaneous detection of resistance to both RIF and INH allows an early diagnosis of an MDR case.…”

Section: Discussionmentioning

confidence: 99%

Use of Genotype MTBDR Assay for Molecular Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis Clinical Strains Isolated in Italy

Miotto

Piana

Penati³

et al. 2006

J Clin Microbiol

105

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Drug-resistant Mycobacterium tuberculosis strains are a real threat to tuberculosis (TB) control worldwide, as strains resistant to major anti-TB drugs have emerged. Multidrug-resistant TB (MDR-TB; resistant at least to rifampin and isoniazid) requires prolonged and expensive chemotherapy, with low cure and high fatality rates (8). In several Eastern European countries economic crisis and health system weaknesses have led to an increase in the numbers of TB cases, together with the establishment of hot spots for MDR-TB. Laboratory surveillance of drug resistance and early identification of resistant strains are critical steps for the beginning of appropriate treatment. Any delay in resistant strain identification jeopardizes the efforts to control the transmission of the disease.Rifampin (RIF) resistance is due to mutation in a relatively small fragment (81 bp) of the rpoB gene encoding for the ␤-subunit of the RNA polymerase (12, 29, 35); isoniazid (INH) resistance is caused by mutations in one of several regions of the katG gene, the inhA regulatory and coding region, and the ahpC-oxyR, ndh, and kasA genes (3,4,18,19,26,29,32,33,36,39). Analysis of strains collected in different countries shows different prevalences of the mutations (24).Easy-to-perform, rapid, and cost-effective assays based on molecular techniques that are suitable for application in clinical mycobacteriology laboratories are necessary to evaluate the presence of genomic mutations conferring resistance. Detection of resistance by conventional methods is inadequate due to the slow growth rate of M. tuberculosis; in addition, direct detection of known mutations could be more reliable in predicting the response to therapy.The Genotype MTBDR (Hain Lifescience, Nehren, Germany) is a new commercial and easy-to-perform assay developed for the detection of RIF and/or INH resistance in TB strains. The test is based on reverse hybridization between amplicons derived from a multiplex PCR and nitrocellulosebound wild-type and mutated probes for the mutations of interest.The aim of the present study was to evaluate Genotype MTBDR as a rapid diagnostic tool to detect rpoB and katG gene mutations that are associated with RIF and INH resistance, respectively, in TB isolates.We tested 206 M. tuberculosis strains isolated in Italy during the past 3 years, including 139 MDR strains and 30 fully susceptible ones. A total of 69 strains were collected from Italian patients, and 137 were obtained from foreign-born people. In order to show that the test is suitable for the direct detection on clinical specimens, we also performed the test on respiratory samples collected from active TB patients. (Table 1). A total of 85% of the MDR strains were isolated from retreatment cases. MATERIALS AND METHODS Strains

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“…Resistance to INH has been associated with alterations in at least four genes, but extensive studies have demonstrated that INH resistance is most frequently associated with a specific mutation in codon 315 of M. tuberculosis catalase peroxidase (katG) gene (13). The prevalence of M. tuberculosis katG mutations varies geographically, but the katG codon 315 mutation is found in between 60 and 90% of the INH-resistant strains (1,2,4,9,10,15). The mechanism of resistance to RIF involves missense mutations in a well-characterized region of the beta subunit of DNA-dependent RNA polymerase (which is encoded by the rpoB gene).…”

Section: Multidrug-resistant (Mdr)mentioning

confidence: 99%

Comparison of Two Commercially Available DNA Line Probe Assays for Detection of Multidrug-Resistant Mycobacterium tuberculosis

et al. 2006

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Multidrug-resistant (MDR) Mycobacterium tuberculosis isolates are resistant to at least isoniazid (INH) and rifampin (RIF), the two most important components of effective antituberculosis therapy. Incorrect use of the drugs, treatment failures, and the transmission of MDR isolates have caused multidrug-resistant tuberculosis (MDR-TB) to become a rapidly increasing health problem in both developed and developing countries (3, 5). Drug susceptibility testing by conventional methods takes several weeks, while early diagnosis of the disease and the rapid identification of resistant strains are essential for efficient treatment and control of the MDR strains.In the last few years, there has been considerable progress in our understanding of the mechanisms of action and of the basis of resistance to the antituberculous drugs, especially resistance to INH and RIF. Resistance to INH has been associated with alterations in at least four genes, but extensive studies have demonstrated that INH resistance is most frequently associated with a specific mutation in codon 315 of M. tuberculosis catalase peroxidase (katG) gene (13). The prevalence of M. tuberculosis katG mutations varies geographically, but the katG codon 315 mutation is found in between 60 and 90% of the INH-resistant strains (1, 2, 4, 9, 10, 15). The mechanism of resistance to RIF involves missense mutations in a well-characterized region of the beta subunit of DNA-dependent RNA polymerase (which is encoded by the rpoB gene). Several studies have shown that more than 95% of RIF-resistant strains harbor a mutation within an 81-bp region of the rpoB gene (8,16,17).Generally, DNA sequencing-based approaches are considered the reference assays for the detection of mutations, but often, they have been found to be too cumbersome for routine use. The commercial strip assay INNO-LiPA Rif. TB (Innogenetics, Ghent, Belgium) has previously been evaluated for the detection of mutations conferring resistance to RIF in M. tuberculosis (7,11,14). The Genotype MTBDR assay (Hain Lifescience GmbH, Nehren, Germany) is a novel kit-based method for the detection of the most common mutations in M. tuberculosis katG and rpoB.The Genotype MTBDR test is based on the same general principle as the INNO-LiPA Rif. TB test, but it has the advantage of being able to detect the presence of mutations in both katG and rpoB simultaneously and thus predict resistance to both INH and RIF (6).Both strip tests are based on reverse hybridization of amplicons (katG in the Genotype MTBDR test and rpoB in both tests) to immobilized, membrane-bound probes covering the wild-type (WT) sequences; the katG 315 mutation (the Genotype MTBDR test); and the rpoB mutations Asp516Val, His526Tyr, His526Asp, and Ser531Leu. The aim of this study was to compare the performances of the Genotype MTBDR test and the INNO-LiPA Rif TB test for the rapid detection of MDR among Finnish and Russian M. tuberculosis isolates. The line probe assay results were compared to the results obtained by conventional sequencing and pheno...

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Contribution of AGC to ACC and other mutations at codon 315 of the katG gene in isoniazid-resistant Mycobacterium tuberculosis isolates from the Middle East

Cited by 36 publications

References 22 publications

Review: The Molecular Basis of Resistance in <i>Mycobaterium tuberculosis</i>

Review: The Molecular Basis of Resistance in <i>Mycobaterium tuberculosis</i>

Use of Genotype MTBDR Assay for Molecular Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis Clinical Strains Isolated in Italy

Comparison of Two Commercially Available DNA Line Probe Assays for Detection of Multidrug-Resistant Mycobacterium tuberculosis

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Contribution of AGC to ACC and other mutations at codon 315 of the katG gene in isoniazid-resistant Mycobacterium tuberculosis isolates from the Middle East

Cited by 36 publications

References 22 publications

Review: The Molecular Basis of Resistance in &lt;i&gt;Mycobaterium tuberculosis&lt;/i&gt;

Review: The Molecular Basis of Resistance in &lt;i&gt;Mycobaterium tuberculosis&lt;/i&gt;

Use of Genotype MTBDR Assay for Molecular Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis Clinical Strains Isolated in Italy

Comparison of Two Commercially Available DNA Line Probe Assays for Detection of Multidrug-Resistant Mycobacterium tuberculosis

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Review: The Molecular Basis of Resistance in <i>Mycobaterium tuberculosis</i>

Review: The Molecular Basis of Resistance in <i>Mycobaterium tuberculosis</i>