scholarly journals A computational perspective on the dynamic behaviour of recurrent drug resistance mutations in the pncA gene from Mycobacterium tuberculosis

RSC Advances ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 2476-2486
Author(s):  
Taimoor Khan ◽  
Abbas Khan ◽  
Syed Shujait Ali ◽  
Shahid Ali ◽  
Dong-Qing Wei
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Causes Of Death ◽  
Dynamic Behaviour ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Computational Perspective

Tuberculosis is still one of the top 10 causes of death worldwide, particularly with the emergence of multidrug-resistant tuberculosis.

scholarly journals Some Synonymous and Nonsynonymous gyrA Mutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDRsl Assays

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Adebisi Ajileye ◽  
Nataly Alvarez ◽  
Matthias Merker ◽  
Timothy M. Walker ◽  
Suriya Akter ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Specific Resistance ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Wild Type ◽  
Resistance Mutations ◽  
Content Type ◽  
Synonymous Mutations ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

ABSTRACT In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.

scholarly journals Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis

2012 ◽  
Vol 56 (6) ◽  
pp. 3047-3053 ◽  
Author(s):  
Lukas Fenner ◽  
Matthias Egger ◽  
Thomas Bodmer ◽  
Ekkehardt Altpeter ◽  
Marcel Zwahlen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Content Type ◽  
Drug Resistance Mutations ◽  
Resistant Strains

ABSTRACTBacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistantMycobacterium tuberculosisisolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains,katGmutations were associated with high-level andinhApromoter mutations with low-level drug resistance. OnlykatG(S315T) (65.6% of all isoniazid-resistant strains) andinhApromoter −15C/T (22.7%) were found in molecular clusters.M. tuberculosislineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6;P< 0.0001). Lineage 1 was associated withinhApromoter −15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7;P= 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages;P< 0.0001). In conclusion,M. tuberculosisdrug resistance mutations were associated with various levels of drug resistance and transmission, andM. tuberculosislineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds inM. tuberculosisdrug resistance.

scholarly journals Scrofula Caused by Multidrug-Resistant Tuberculosis

2020 ◽  
Author(s):  
Bárbara Pedro ◽  
Liliana Alves ◽  
Rita Magano ◽  
Tomás Nunes ◽  
Nuno Marques
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
Causes Of Death ◽  
Cervical Lymphadenopathy ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Immunodeficiency Virus ◽  
Mdr Tb ◽  
Hiv Negative

Tuberculosis (TB) is one of the top 10 causes of death worldwide. Multidrug-resistant tuberculosis (MDR-TB) occurs when at the minimum there is resistance to isoniazid and rifampin. Prevention of new infections of Mycobacterium tuberculosis and progression to TB disease is critical to reduce the burden and mortality of this disease. We present the case of a 73-year-old human immunodeficiency virus (HIV)-negative female who presented with cervical lymphadenopathy and who was diagnosed with MDR-TB.

Genotypic analysis of multidrug-resistant Mycobacterium tuberculosis isolates from Monterrey, Mexico

2004 ◽  
Vol 53 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Srinivas V. Ramaswamy ◽  
Shu-Jun Dou ◽  
Adrian Rendon ◽  
Zhenhua Yang ◽  
M. Donald Cave ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Secondary Resistance ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Genotypic Analysis ◽  
Mdr Tb

Thirty-seven multidrug-resistant and 13 pan-susceptible isolates of Mycobacterium tuberculosis were analysed for the diversity of genotypes associated with known drug-resistance mechanisms. The isolates were obtained from patients attending a university tuberculosis clinic in Monterrey, Mexico. A total of 25 IS6110-RFLP patterns were obtained from the multidrug-resistant tuberculosis (MDR-TB) isolates. Approximately 65 % of the MDR-TB isolates were attributed to secondary resistance. Different drug-susceptibility patterns were seen with the clustered isolates. The percentage of isolates resistant to isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (STR) was 100, 97.3, 48.7 and 67.6, respectively. The most common resistance-associated polymorphisms for the four drugs were as follows: INH, Ser315Thr (67.6 %) in katG; RIF, Ser450Leu (41.7 %) in rpoB; EMB, Met306Ile/Val/Leu (66.7 %) in embB; and STR, Lys43Arg (24 %) in rpsL. Drug-resistance-associated mutations were similar to changes occurring in isolates from other areas of the world, but unique, previously unreported, mutations in katG (n = 5), rpoB (n = 1) and rrs (n = 3) were also identified.

Emergence of Extensive Drug Resistance during Treatment for Multidrug-Resistant Tuberculosis

2008 ◽  
Vol 359 (22) ◽  
pp. 2398-2400 ◽  
Author(s):  
Helen S. Cox ◽  
Caterina Sibilia ◽  
Silke Feuerriegel ◽  
Stobdan Kalon ◽  
Jonny Polonsky ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Extensive Drug Resistance

scholarly journals Use of fluorescein diacetate (FDA) staining to detect viable Mycobacterium tuberculosis

2012 ◽  
Vol 11 (4) ◽  
pp. 322-330 ◽  
Author(s):  
Shamima Islam ◽  
Farjana Rahman ◽  
Saurab Kisore Munshi ◽  
Jewel Ahmed ◽  
S M Mostafa Kamal ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Treatment Failure ◽  
Medical Science ◽  
Multidrug Resistant ◽  
Fluorescein Diacetate ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Auramine O

Objective: Drug resistant tuberculosis has long been a common problem prevailing in developing countries including Bangladesh. Present study focused on the rapid identification of live Mycobacterium tuberculosis among treatment failure cases.Materials and Methods: Sputum samples from a total of 100 category-I and category-II treatment failure cases, assumed as multidrug resistant tuberculosis, were studied through fluorescein diacetate (FDA) staining under light emitting diode (LED) fluorescence microscope. Considering culture method as gold standard, we also compared the results of FDA staining with that of auramine O staining.Results: A total of 85% acid-fast bacilli were detected by FDA staining, 82% by auramine O staining and a total of 85% isolates were detected in Lowenstein-Jensen (LJ) culture. The sensitivity of FDA staining (96.47%) was estimated to be slightly higher than that of auramine O staining (91.76%). Moreover,76.47% cases were detected as multidrug resistant tuberculosis (MDR-TB). Conclusion: Taken together, FDA staining method has been proposed to be appropriate for the rapid diagnosis of drug resistant tuberculosis. DOI: http://dx.doi.org/10.3329/bjms.v11i4.12605 Bangladesh Journal of Medical Science Vol. 11 No. 04 Oct’12

scholarly journals Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

2017 ◽  
Vol 8 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Aleksandr I. Ilin ◽  
Murat E. Kulmanov ◽  
Ilya S. Korotetskiy ◽  
Marina V. Lankina ◽  
Gulshara K. Akhmetova ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Genetic Heterogeneity ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
General Increase ◽  
Drug Induced ◽  
Mdr Tb ◽  
Resistant Strains

Emergence of multidrug resistant strains ofMycobacterium tuberculosis(MDR-TB) threatens humanity. This problem was complicated by the crisis in development of new anti-tuberculosis antibiotics. Induced reversion of drug resistance seems promising to overcome the problem. Successful clinical trial of a new anti-tuberculosis nanomolecular complex FS-1 has demonstrated prospectively of this approach in combating MDR-TB. Several clinical MDR-TB cultures were isolated from sputum samples prior and in the process of the clinical trial. Every isolate was tested for susceptibility to antibiotics and then they were sequenced for comparative genomics. It was found that the treatment with FS-1 caused an increase in the number of antibiotic susceptible strains among Mtb isolates that was associated with a general increase of genetic heterogeneity of the isolates. Observed impairing of phthiocerol dimycocerosate biosynthesis by disruptive mutations inppsACDsubunits indicated a possible virulence remission for the sake of persistence. It was hypothesized that the FS-1 treatment eradicated the most drug resistant Mtb variants from the population by aggravating the fitness cost of drug resistance mutations. Analysis of distribution of these mutations in the global Mtb population revealed that many of them were incompatible with each other and dependent on allelic states of many other polymorphic loci. The latter discovery may explain the negative correlation between the genetic heterogeneity of the population and the level of drug tolerance. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that previously was predicted theoretically.

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