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T CELL EPITOPES OF THE ESXA FULL GENE OF MYCOBACTERIUM TUBERCULOSIS FROM SPUTUM OF MDR-TB PATIENTS.

ABSTRACT: Background:In 2015, World Health Organization (WHO) discovered 10.4 million tuberculosis (TB) cases around the world. Multidrug-resistant tuberculosis (MDR-TB) became a threat because it has high mortality number. There were 480,000 new MDR-TB cases in 2015. Based on those problems, diagnostic development to detect M. tuberculosis rapidly and accurately is needed. The importance of detecting epitope expression of esxA full gene because there was a potential of complexity over the protein structure and might affect the protein concentration. By knowing epitope prediction, there's an expectation that it can help the development of TB diagnostic. This research was aimed to determine the T cell epitope prediction of esxA full gene from MDR-TB patients. Material and Methods:Total of 24 MDR-TB sputum isolate from TB patients at Dr. Soetomo Hospital were collected from September to December 2016. Samples were confirmed as MDR-TB using GeneXpert and Bactec MGIT 960. Those samples tested using PCR targeted 580 bp of esxA gene and sequencing. Gene sequence was aligned against wild type using Bioedit program version 7.2.5 and NCBI BLAST. T cell epitope prediction was analyzed by GENETYX version 10. Results:Epitope predictions that could be obtained were IEAAAS, ASAIQG, VTSIHS, TKLAAA, VTGMFA based IAd Pattern Position and EAAAS based Rothbard/Taylor Pattern Position. Those prediction epitopes can determine the severity of disease, therefore full gene of esxA could be used as diagnostic target. Conclusion:This research discovered five specific T cell epitope prediction based on IAd Pattern Position and one epitope prediction according to Rothbard/Taylor Pattern Position.

SUBMITTER: Dewi DNSS

PROVIDER: S-EPMC6085733 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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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.

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T CELL EPITOPES OF THE ESXA FULL GENE OF MYCOBACTERIUM TUBERCULOSIS FROM SPUTUM OF MDR-TB PATIENTS.

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