scholarly journals Frequency of mutational changes in the embB among the ethambutol-resistant strains of Mycobacterium tuberculosis in Iran

2016 ◽  
Vol 10 (04) ◽  
pp. 363-368 ◽  
Author(s):  
Faranak Rezaei ◽  
Mehri Haeili ◽  
Parviz Mohajeri ◽  
Abdolrazagh Hashemi Shahraki ◽  
Abbas Ali Imani Fooladi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Control Program ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Molecular Tests ◽  
Resistant Tuberculosis ◽  
Resistant Strains ◽  
Embb Gene

Introduction: Early detection of drug resistant tuberculosis is one of the main priorities of TB control program. Ethambutol (EMB) is a first-line anti-TB drug that is effective for preventing treatment failures caused by Mycobacterium tuberculosis strains that are resistant to other drugs. The aim of this study was to sequence the embB gene to characterize the mutations causing resistance to EMB and to analyze the relationship between bacterial genotype and EMB resistance among M. tuberculosis isolates in Iran. Methodology: A total of 20 M. tuberculosis isolates comprising 10 multidrug-resistant (MDR) and 10 non-MDR isolates, recovered from TB patients in four regions: Tehran, Isfahan, Zahedan, Khorasan, were analyzed. Mutational profiling was performed by amplifying and sequencing the embB gene. Spoligotyping was carried out to characterize the bacterial genotype. Results: Phenotypic EMB resistance was found in 13 strains. Mutations affecting ethambutol resistance-determining region (ERDR) of the embB were identified in 6 of 13 EMB-resistant isolates. The majority of these mutations resulted in amino acid substitution at position 306 (M306V). A novel mutation at codon 366 was identified (S366L) in one isolate. Ural was the most predominant genotype in the studied population. Beijing genotype was associated with both MDR and EMB resistance in which all mutations occurred at codon 306 of the embB gene. Conclusion: A significant association between Beijing genotype and EMB resistance was found, mainly due to mutations at embB306. Results of this study can be used as a basis to develop or improve rapid molecular tests to monitor drug-resistant strains in this country.

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 Gene Mutation Characteristics and Cluster Analysis of Multidrug-Resistant Mycobacterium Tuberculosis in Urumqi

2021 ◽  
Author(s):  
Jiandong Yang ◽  
Rayibai Yadikaer ◽  
Yanggui Chen ◽  
Li Ma ◽  
Yaoqin Lu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Resistance Gene ◽  
Gene Mutation ◽  
Multidrug Resistant ◽  
Biological Characteristics ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Resistant Strains ◽  
And Cluster Analysis ◽  
Drug Resistant Strains

Abstract Objective To understand the molecular biological characteristics of multidrug-resistant Mycobacterium tuberculosis in Urumqi by the analysis of gene mutation and clustering of multidrug-resistant Mycobacterium tuberculosis in Urumqi, to provid theoretical basis for the prevention and control of multidrug-resistant tuberculosis in the future. Methods The tuberculosis patients who were diagnosed, registered, cultured positive Mycobacterium tuberculosis and over 16 years old in Urumqi were studied. Geno Type MTBDR plus Assay and MIRU-VNTR were used to analysis the gene mutation and clustering of multidrug-resistant mycobacterium tuberculosis in Urumqi. Result Mutation gene included Isoniazid resistance gene katG 315; Rifampicin resistance gene rpoB 526, 531; Ethambutol resistance gene embB 206; Streptomycin resistance gene rpsL 43 and RRs 1401; Ofloxacin resistance gene gyrA 74, 90, 91 and 94. It was shown that the Beijing genotype was predominant (49.530%) among these319strains. There were 14 strains multi-drug resistant strains, it was predominant (73.684%) of multi-drug resistant strains. Multi-drug resistant prevalence of Beijing strains was 8.861%. The clustering rate of MDR-TB was 5.263% in Urumqi. Conclusion Molecular biological characteristics of multidrug-resistant Mycobacterium tuberculosis have some particularities in Urumqi. Therefore, modern molecular epidemiological techniques such as molecular biology and DNA fingerprinting can be used to improve the speed of diagnosis and to carry out case tracking and source investigation.

scholarly journals Profil De Résistance Des Mycobabcterium Tuberculosis Des Malades En Retraitement Dans La Région De Haute Matsiatra, Madagascar

2017 ◽  
Vol 13 (18) ◽  
pp. 465
Author(s):  
Ravahatra Kiady ◽  
Rakotondrabe Iantsotiana Davidson ◽  
Rasoafaranirina Marie Odette ◽  
Tiaray Harison Michel ◽  
Nandimbiniaina Anjara ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Control Program ◽  
Multidrug Resistant ◽  
University Hospital ◽  
Tuberculosis Control ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Study Results ◽  
Resistant Strains ◽  
The University

Introduction: Relapse, failure and defaulted treatment are a risk factor for Mycobacterium tuberculosis resistance to anti-tuberculosis. The objective of our study is to determine the resistance profile of Mycobacterium tuberculosis of patients in retreatment at the Haute Matriatra area. Method: This is a retrospective, descriptive study carried out on the basis of the data contained in the register of the Haute Matsiatra Regional Tuberculosis Laboratory of the University Hospital of Fianarantsoa, from May 2014 to December 2016 (31 months). We included patients with retreatment in the study. Results: We found 138 patients in retreatment. The average age was 39.32 years with a sex ratio of 2.11. Resistance to Rifampicin and Isoniazid was respectively 2.17% and 2.82%, The prevalence of multidrug-resistant tuberculosis was 0.72%. Conclusion: Tuberculosi resistance, monoresistance or multidrug resistance is a reality in the region of Haute Matsiatra with a prevalence that is still low, reflecting the effectiveness of the tuberculosis control program. However, monoresistances require special attention and monitoring to avoid the emergence of multidrug resistant strains.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

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 Tuberculose Multirresistente por Estirpes da Família Beijing, em Doentes de Lisboa, Portugal: Estudo Preliminar

2017 ◽  
Vol 30 (3) ◽  
pp. 175 ◽  
Author(s):  
Fernando Maltez ◽  
Teresa Martins ◽  
Diana Póvoas ◽  
João Cabo ◽  
Helena Peres ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Past History ◽  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Drug Resistant ◽  
Beijing Family ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Number Of Patients ◽  
Drug Resistant Strains

Introduction: Beijing family strains of Mycobacterium tuberculosis are associated with multidrug-resistance. Although strains of the Lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the Beijing family. However, the features of patients from whom they were isolated, are not yet known.Material and Methods: Retrospective study involving 104 multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, from the same number of patients, isolated and genotyped between 1993 and 2015 in Lisbon. We assessed the prevalence of strains of both families and the epidemiologic and clinical features of those infected with Beijing family strains.Results: Seventy-four strains (71.2%) belonged to the Lisboa family, 25 (24.0%) showed a unique genotypic pattern and five (4.8%) belonged to the Beijing family, the latter identified after 2009. Those infected with Beijing family strains were angolan (n = 1), ukrainian (n = 2) and portuguese (n = 2), mainly young-aged and, four of five immunocompetent and with no past history of tuberculosis. All had multidrug-resistant tuberculosis. We did not find any distinctive clinical or radiological features, neither a predominant resistance pattern. Cure rate was high (four patients).Discussion: Although the number of infected patients with Beijing strains was small, it suggests an important proportion of primary tuberculosis, a potential for transmission in the community but also a better clinical outcome when compared to other reported strains, such as W-Beijing and Lisboa.Conclusion: Although Lisboa family strains account for most of the multidrug and extensively drug-resistant tuberculosis cases in Lisbon area, Beijing strains are transmitted in the city and might change the local characteristics of the epidemics.

scholarly journals Bazedoxifene Suppresses Intracellular Mycobacterium tuberculosis Growth by Enhancing Autophagy

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Qi Ouyang ◽  
Kehong Zhang ◽  
Dachuan Lin ◽  
Carl G. Feng ◽  
Yi Cai ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
New Host ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Receptor Modulator ◽  
Resistant Tuberculosis ◽  
Negative Side Effects

ABSTRACT Tuberculosis (TB) is still the leading killer caused by Mycobacterium tuberculosis infection. There is a clear need for new treatment strategy against TB. It has been reported that tamoxifen, known as a selective estrogen receptor modulator (SERM), exhibits antimycobacterial activity and inhibits M. tuberculosis growth in macrophages. However, it remains unknown whether such antimicrobial activity is a general property of all SERMs and how it works. In this study, we identified that bazedoxifene (BZA), a newer SERM, inhibits intracellular M. tuberculosis growth in macrophages. BZA treatment increases autophagosome formation and LC3B-II protein expression in M. tuberculosis-infected macrophages. We further demonstrated that the enhancement of autophagy by BZA is dependent on increased reactive oxygen species (ROS) production and associated with phosphorylation of Akt/mTOR signaling. In summary, our data reveal a previously unappreciated antimicrobial function of BZA and suggest that future investigation focusing on the mechanism of action of SERMs in macrophages may lead to new host-directed therapies against TB. IMPORTANCE Since current strategies for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have low efficacy and highly negative side effects, research on new treatments including novel drugs is essential for curing drug-resistant tuberculosis. Host-directed therapy (HDT) has become a promising idea to modulate host cell responses to enhance protective immunity against pathogens. Bazedoxifene (BZA), which belongs to a new generation of SERMs, shows the ability to inhibit the growth of M. tuberculosis in macrophages and is associated with autophagy. Our findings reveal a previously unrecognized antibacterial function of BZA. We propose that the mechanism of SERMs action in macrophages may provide a new potential measure for host-directed therapies against TB.

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