Gene expression analysis of two extensively drug-resistant tuberculosis isolates show that two-component response systems enhance drug resistance

Tuberculosis ◽  
2015 ◽  
Vol 95 (3) ◽  
pp. 303-314 ◽  
Author(s):  
Guohua Yu ◽  
Zhenling Cui ◽  
Xian Sun ◽  
Jinfu Peng ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Resistance ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Two Component ◽  
Response Systems

scholarly journals Evolution and Transmission Patterns of Extensively Drug-Resistant Tuberculosis in China

2014 ◽  
Vol 59 (2) ◽  
pp. 818-825 ◽  
Author(s):  
Feifei Wang ◽  
Lingyun Shao ◽  
Xiaoping Fan ◽  
Yaojie Shen ◽  
Ni Diao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Variable Number Tandem Repeat ◽  
Resistance Mutation ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTThe emergence and transmission of extensively drug-resistant tuberculosis (XDR-TB) pose an increasing threat to global TB control. This study aimed to identify the patterns of evolution and transmission dynamics of XDR-TB in populations in a region of China where TB is highly endemic. We analyzed a total of 95 XDR-TB isolates collected from 2003 to 2009 in Chongqing, China. Eight drug resistance genes covering 7 drugs that define XDR-TB were amplified by PCR followed by DNA sequencing. Variable-number tandem repeat 16-locus (VNTR-16) genotyping and genotypic drug resistance profiles were used to determine the evolution or transmission patterns of XDR-TB strains. Our results indicated that the Beijing genotype was predominant (85/95 [89.5%]) in XDR-TB strains, and as many as 40.0% (38/95) of the isolates were distributed into 6 clusters based on VNTR-16 genotyping and drug resistance mutation profiles. All isolates of each cluster harbored as many as six identical resistance mutations in the drug resistance genesrpoB,katG,inhApromoter,embB,rpsL, andgidB. Among the nine cases with continuous isolates from multidrug-resistant (MDR) to XDR-TB, 4 cases represented acquired drug resistance, 4 cases were caused by transmission, and 1 case was due to exogenous superinfection. The XDR-TB epidemic in China is mainly caused by a high degree of clonal transmission, but evolution from MDR to XDR and even superinfection with a new XDR strain can also occur.

scholarly journals Drug resistance profile among multi-drug resistant tuberculosis patients at diagnosis and correlation with history of anti-tubercular treatment in a tertiary care center

2019 ◽  
Vol 6 (6) ◽  
pp. 1918
Author(s):  
Rahul Kumar ◽  
Rajiv Garg ◽  
Silpa Kshetrimayum ◽  
Amita Jain
Keyword(s):  
Drug Resistance ◽  
Drug Sensitivity ◽  
Drug Resistant ◽  
Second Line ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Primary Drug Resistance ◽  
Mdr Tb ◽  
History Of

Background: Drug Resistant Tuberculosis (DR-TB) is a major threat to the realization of the goal of a TB free world in the near future. It is important to study the reasons for the increasing number of such cases so that effective action can be taken to control this growing epidemic.Methods: Sputum from 36 patients diagnosed with acquired pulmonary Multidrug Resistant Tuberculosis (MDR-TB) were subjected to first- and second-line Drug Sensitivity Testing (DST) after liquid culture in mycobacterium growth Indicator Tube (MGIT). Primary MDR-TB cases were excluded. The relation of the drug sensitivity profile with the history of prior treatment taken was statistically analysed.Results: Majority of the patients had received appropriate treatment, and most had adhered to prescribed treatment. Among the 36 patients, 24(66.7%) were found to be Pre-Extensively Drug Resistant (Pre-XDR-TB) and 4(11.1%) were extensively drug resistant XDR-TB cases. Inappropriate prescription of fluoroquinolone (FQ) was found to be most common. Prior intake of any drug was not found to significantly affect subsequent resistance to that drug.Conclusions: Fluoroquinolone resistance is quite common in patients with DR-TB (66.7%). This study did not find the prior use of FQ or any other drug to significantly affect subsequent resistance to the drug. Primary drug resistance is thus a major concern. 11.1% patients were found to be XDR-TB cases. Hence DST for first- and second-line drugs should be done at the time of diagnosis to avoid failure of treatment with a predesigned regimen.

scholarly journals Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis

2012 ◽  
Vol 42 (1) ◽  
pp. 169-179 ◽  
Author(s):  
Giovanni Battista Migliori ◽  
Giovanni Sotgiu ◽  
Neel R. Gandhi ◽  
Dennis Falzon ◽  
Kathryn DeRiemer ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

scholarly journals Issues of Tuberculosis Drug-Resistance in Kharkiv Region and in Ukraine

2019 ◽  
pp. 24-28
Author(s):  
O.S. Shevchenko ◽  
O.O. Pohorielova
Keyword(s):  
Drug Resistance ◽  
Statistical Processing ◽  
Multidrug Resistant ◽  
Study Data ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Microsoft Office

Background. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis remain severe epidemic problems in the world. That’s why the purpose of our study was to investigate the dynamics of the incidence of multidrug-resistant and extensively drug-resistant tuberculosis, the structure of cases and the effectiveness of treatment in this category of patients in the Kharkiv region and in Ukraine. Materials and methods. To perform the study, data from reporting forms No. 4-2 (TB 07 – MDR TB), No. 8-6 (TB 08) and data from analytical and statistical reference books “Tuberculosis in Ukraine” were used. Statistical processing of information was carried out using Statistica 7.0, Microsoft Office Excel 2007. Results. We found a relatively consistently high incidence rate, prevalence of tuberculosis recurrences among patients with drug-resistant tuberculosis, an increase in the proportion of extensively-drug resistance in patients with treatment failure and interrupted treatment, and low effectiveness of treatment of multidrug-resistant and extensively drug-resistant tuberculosis in patients with repeated cases of treatment. Conclusions. The obtained data once again emphasizes the need for the selection of adequate schemes for antituberculosis chemotherapy and control of anti-tuberculosis drugs.

scholarly journals Early Detection of Emergent Extensively Drug-Resistant Tuberculosis by Flow Cytometry-Based Phenotyping and Whole-Genome Sequencing

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Max R. O’Donnell ◽  
Michelle H. Larsen ◽  
Tyler S. Brown ◽  
Paras Jain ◽  
Vanisha Munsamy ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Genome Sequencing ◽  
Low Frequency ◽  
Whole Genome ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTA critical gap in tuberculosis (TB) treatment is detection of emergent drug resistance. We hypothesized that advanced phenotyping with whole-genome sequencing (WGS) will detect low-frequencyMycobacterium tuberculosisdrug resistance. We assessed a reporter mycobacteriophage (Φ2GFP10)in vitroto detect drug-resistant subpopulations and predictM. tuberculosisbactericidal activity in this pilot study. Subsequently, we prospectively studied 20 TB patients with serial Φ2GFP10, Xpert MTB/RIF, andM. tuberculosisculture through end of treatment. WGS was performed, and single nucleotide polymorphisms (SNPs) were examined to detect mixed infection in selectedM. tuberculosisisolates. ResistantM. tuberculosisisolates were detected at 1:100,000, and changes in cytometry-gated events were predictive ofin vitroM. tuberculosisbactericidal activity using the Φ2GFP10 assay. Emergent drug resistance was detected in one patient by Φ2GFP10 at 3 weeks but not by conventional testing (M. tuberculosisculture and GeneXpert). WGS revealed a phylogeographically distinct extensively drug-resistant tuberculosis (XDR-TB) genome, identical to an XDR-TB isolate from the patient’s spouse. Variant lineage-specific SNPs were present early, suggesting mixed infection as the etiology of emergent resistance with temporal trends providing evidence for selection during treatment. Φ2GFP10 can detect low-frequency drug-resistantM. tuberculosisand with WGS characterize emergentM. tuberculosisresistance. In areas of high TB transmission and drug resistance, rapid screening for heteroresistance should be considered.

scholarly journals Increasing Drug Resistance in Extensively Drug-Resistant Tuberculosis, South Africa

2011 ◽  
Vol 17 (3) ◽  
pp. 510-513 ◽  
Author(s):  
N. Sarita Shah ◽  
Jessica Richardson ◽  
Prashini Moodley ◽  
Salona Moodley ◽  
Palav Babaria ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant
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