Dataset Information

Virtual screening of a MDR-TB WhiB6 target identified by gene expression profiling.

ABSTRACT: Multidrug resistance in M. tb has become a huge global problem due to drug resistance. Hence, the treatment remains a challenge, even though short term chemotherapy is available. Therefore, it is of interest to identify novel drug targets in M.tb through gene expression profiling complimented by a subtractive proteome model. WhiB6 is a transcriptional regulator protein and a known drug resistant marker that is critical in the secretion dependent regulation of ESX-1, which is specialized for the deployment of host membrane-targeting proteins. The WhiB6 protein structure was modelled ab initio and was docked with a library of 173 phytochemicals with potential antituberculosis activity to the identified drug marker to find novel lead molecules. UDP-galactopyranose and GDP-L-galactose were identified to be potential lead molecules to inhibit the target WhiB6. The results were compared with the first line drugs for MDR-TB by docking with WhiB6. Data showed that Ethambutol showed better binding ability to WhiB6 but the afore mentioned top ranked phytochemicals were found to be better candidate molecules. The chosen candidate lead molecules should be further validated by suitable in vitro or in vivo investigation.

SUBMITTER: Vijayaraj M

PROVIDER: S-EPMC6822516 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Virtual screening of a MDR-TB WhiB6 target identified by gene expression profiling.

Vijayaraj Mahalakshmi M Abhinand P A PA Ragunath P K PK

Bioinformation 20190905 8

Multidrug resistance in M. tb has become a huge global problem due to drug resistance. Hence, the treatment remains a challenge, even though short term chemotherapy is available. Therefore, it is of interest to identify novel drug targets in M.tb through gene expression profiling complimented by a subtractive proteome model. WhiB6 is a transcriptional regulator protein and a known drug resistant marker that is critical in the secretion dependent regulation of ESX-1, which is specialized for the ...[more]

PMID: 31719765

Similar Datasets

Project description:BackgroundThe Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support.ObjectivesTo assess whether CBMDR-TBC project's support improved treatment initiation.MethodsIn this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as "receiving support" if date of project initiation in patient's township was before the date of diagnosis and "not receiving support", if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation.ResultsOf 456 patients, 57% initiated treatment: 64% and 56% among patients "receiving support (n = 208)" and "not receiving support (n = 228)" respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients "receiving support" and 50 (26,101) among patients "not receiving support". After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients "receiving support" had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients "not receiving support". In addition, age 15-54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation.ConclusionReceiving support under CBMDR-TBC project improved treatment initiation: it not only improved the proportion initiated but also reduced time to treatment initiation. We also recommend improved tracking of all diagnosed patients as early as possible.

Project description:Beijing strains of Mycobacterium tuberculosis (lineage 2) have been associated with drug-resistance and transmission of tuberculosis worldwide. Most of the Beijing strains identified in the Colombian Pacific coast have exhibited a multidrug resistant (MDR) phenotype. We sought to evaluate the clonality and sublineage of Beijing strains circulating in Southwestern Colombia. Thirty-seven Beijing strains were identified through spoligotyping out of 311 clinical isolates collected in 9 years from 2002-2010. Further analysis by MIRU-VNTR 24 loci was conducted for the Beijing strains. For sublineage classification, deletions of RD105, RD207, and RD131 and point mutations at fbpB, mutT2, and acs were evaluated. Drug-resistance associated mutations to first- and second-line anti-TB drugs were also evaluated. Additionally, two Beijing strains were Illumina-whole genome sequenced (one MDR and one drug-susceptible). Among the 37 Beijing strains characterized, 36 belonged to the SIT190 type from which 28 were MDR, four pre-extensively drug resistant (XDR) TB, and four XDR-TB. The remaining strain was SIT1 and drug susceptible. MIRU-VNTR analysis allowed the identification of three Beijing clusters and two unique strains. Beijing strains were confirmed as "modern" sublineage. The mutations rpoB S531L and katG S315T were the most common among MDR strains. Moreover, the two strains evaluated by whole genome sequencing (WGS) shared most of the genetic features with the sublineage 2.2.1 "modern" Beijing previously characterized from Asian strains. WGS analysis of the MDR strain revealed the presence of eight SNPs previously reported in other MDR "Beijing-like" strains from Colombia. The presence of "modern" Beijing strains in Southwestern Colombia, most of them with MDR phenotype, suggests a different origin of this M. tuberculosis sublineage compared to other Beijing strains found in neighboring South American countries. This work may serve as a genetic baseline to study the evolution and spread of M. tuberculosis Beijing strains in Colombia, which play an important role in the propagation of MDR-TB.

Dataset Information

Virtual screening of a MDR-TB WhiB6 target identified by gene expression profiling.

Publications

Virtual screening of a MDR-TB WhiB6 target identified by gene expression profiling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets