Dataset Information

Proteome analysis of the M. tuberculosis Beijing B0/W148 cluster

ABSTRACT: The main project purpose is to investigate the fundamental physiological state of M. tuberculosis (MTB) during the infection and the mycobacterial response within the infected host tissue, human lung. High-throughput proteomic analysis of MTB cells will be involved to solve this problem. The description of pattern of proteins expressed in MTB cells extracted directly from clinical material of patients with tuberculosis defines the main novelty of the given project. Undoubtedly, the intermediate project results describing the features of MTB strains proteome in vitro will also be essential for the global scientific community.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mycobacterium Tuberculosis Sp1 Mycobacterium Tuberculosis Sp13 Mycobacterium Tuberculosis Mycobacterium Tuberculosis Sp7 Mycobacterium Tuberculosis Sp22 Mycobacterium Tuberculosis Sp10 Mycobacterium Tuberculosis H37rv

SUBMITTER: Ilya Altukhov

LAB HEAD: Elena Ilina

PROVIDER: PXD002542 | Pride | 2016-07-06

REPOSITORIES: Pride

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Proteome analysis of the Mycobacterium tuberculosis Beijing B0/W148 cluster.

Bespyatykh Julia J Shitikov Egor E Butenko Ivan I Altukhov Ilya I Alexeev Dmitry D Mokrousov Igor I Dogonadze Marine M Zhuravlev Viacheslav V Yablonsky Peter P Ilina Elena E Govorun Vadim V

Scientific reports 20160630

Beijing B0/W148, a "successful" clone of Mycobacterium tuberculosis, is widespread in the Russian Federation and some countries of the former Soviet Union. Here, we used label-free gel-LC-MS/MS shotgun proteomics to discover features of Beijing B0/W148 strains that could explain their success. Qualitative and quantitative proteome analyses of Beijing B0/W148 strains allowed us to identify 1,868 proteins, including 266 that were differentially abundant compared with the control strain H37Rv. To p ...[more]

PMID: 27356881

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Project description:The identification of multidrug resistant (MDR), extensively and totally drug resistant Mycobacterium tuberculosis (Mtb), in vulnerable sites such as Mumbai, is a grave threat to the control of tuberculosis. The current study aimed at explaining the rapid expression of MDR in Directly Observed Treatment Short Course (DOTS) compliant patients, represents the first study comparing global transcriptional profiles of 3 pairs of clinical Mtb isolates, collected longitudinally at initiation and completion of DOTS. While the isolates were drug susceptible (DS) at onset and MDR at completion of DOTS, they exhibited identical DNA fingerprints at both points of collection. The whole genome transcriptional analysis was performed using total RNA from H37Rv and 3 locally predominant spoligotypes viz. MANU1, CAS and Beijing, hybridized on MTBv3 (BuG@S) microarray, and yielded 36, 98 and 45 differentially expressed genes respectively. Genes encoding transcription factors (sig, rpoB), cell wall biosynthesis (emb genes), protein synthesis (rpl) and additional central metabolic pathways (ppdK, pknH, pfkB) were found to be down regulated in the MDR isolates as compared to the DS isolate of the same genotype. Up regulation of drug efflux pumps, ABC transporters, trans-membrane proteins and stress response transcriptional factors (whiB) in the MDR isolates was observed. The data indicated that Mtb, without specific mutations in drug target genes may persist in the host due to additional mechanisms like drug efflux pumps and lowered rate of metabolism. Furthermore this population of Mtb, which also showed reduced DNA repair activity, would result in selection and stabilization of spontaneous mutations in drug target genes, causing selection of a MDR strain in the presence of drug pressures. Efflux pump such as drrA may play a significant role in increasing fitness of low level drug resistant cells and assist in survival of Mtb till acquisition of drug resistant mutations with least fitness cost. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-134]

			Action	DRS
	H37Rv_1.dat	Other
	H37Rv_1.dat-pride.pride.mgf.gz	Mgf
	H37Rv_1.dat-pride.pride.mztab.gz	Mztab
	H37Rv_1.dat-pride.xml.gz	Xml
	H37Rv_1.mgf	Mgf