Abstract
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 predict the biological effects of the observed differences in protein abundances, we performed Gene Ontology analysis together with analysis of protein-DNA interactions using a gene regulatory network. Our results demonstrate that Beijing B0/W148 strains have increased levels of enzymes responsible for long-chain fatty acid biosynthesis, along with a coincident decrease in the abundance of proteins responsible for their degradation. Together with high levels of HsaA (Rv3570c) protein, involved in steroid degradation, these findings provide a possible explanation for the increased transmissibility of Beijing B0/W148 strains and their survival in host macrophages. Among other, we confirmed a very low level of the SseA (Rv3283) protein in Beijing B0/W148 characteristic for all «modern» Beijing strains, which could lead to increased DNA oxidative damage, accumulation of mutations, and potentially facilitate the development of drug resistance.
Highlights
Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB) and, according to the Global Tuberculosis Report produced by the World Health Organization (WHO), nine million people had TB in 2014 and 1.5 million died because of the disease[1]
Relatively few studies have focused on the proteomes of specific genetic families of MTB and only two reports characterizing the proteomes of Beijing family strains have been published
Seven Beijing B0/W148 cluster strains were selected for inclusion in the proteomic study
Summary
Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB) and, according to the Global Tuberculosis Report produced by the World Health Organization (WHO), nine million people had TB in 2014 and 1.5 million died because of the disease[1]. A recent systematic and critical review summarized various biological and phylogenetic features of the Beijing B0/W148 cluster[6] Strains of this cluster possess unique pathogenic properties, including stronger association with multidrug resistance and higher levels of clustering (i.e. higher transmissibility) compared with other Beijing variants, as demonstrated by a meta-analysis of studies from across the former Soviet Union[6]. Beijing variant MTB strains have a unique genome organization; recently, we reported large scale chromosomal inversions spanning 350 and 550 kb segments of the chromosome[9]. The presence of these inversions in Beijing B0/W148 cluster strains was confirmed by PCR, sequencing, and RFLP analysis. We have applied a label-free gel-LC-MS/MS shotgun proteomics approach for empirical ‘bottom-up’ exploration of Beijing B0/W148 strains
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