Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates

被引:18
作者
Heunis, Tiaan [1 ]
Dippenaar, Anzaan [1 ]
Warren, Robin M. [1 ]
van Helden, Paul D. [1 ]
van der Merwe, Ruben G. [1 ]
van Pittius, Nicolaas C. Gey [1 ]
Pain, Arnab [2 ]
Sampson, Samantha L. [1 ]
Tabb, David L. [1 ]
机构
[1] Stellenbosch Univ, Fac Med & Hlth Sci, DST NRF Ctr Excellence Biomed TB Res, SAMRC Ctr TB Res,Div Mol Biol & Human Genet, ZA-7505 Cape Town, South Africa
[2] King Abdullah Univ Sci & Technol, BESE Div, Pathogen Genom Lab, Thuwal 23955, Saudi Arabia
基金
英国医学研究理事会; 新加坡国家研究基金会;
关键词
Mycobacterium tuberculosis; clinical microbial proteogenomics; variant peptides; strain variation; MASS-SPECTROMETRY; PROTEIN IDENTIFICATION; GENOME SEQUENCE; DISCOVERY; PROTEOMICS; DATABASES; REGIONS; DISSEMINATION; STRATEGIES; DIAGNOSIS;
D O I
10.1021/acs.jproteome.7b00483
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of the utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study, we integrated wholegenome sequencing and mass spectrometry (GeLC MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M. tuberculosis Latin American-Mediterranean isolates. Using this approach, we identified 59 peptides containing single amino acid variants, which covered similar to 9% of all coding nonsynonymous single nucleotide variants detected by whole-genome sequencing. Furthermore, we identified 29 distinct peptides that mapped to a hypothetical protein not present in the M. tuberculosis H37Rv reference proteome. Here, we provide evidence for the expression of this protein in the clinical M. tuberculosis SAWC3651 isolate. The strain-specific databases enabled confirmation of genomic differences (i.e., large genomic regions of difference and nonsynonymous single nucleotide variants) in these two clinical M. tuberculosis isolates and allowed strain differentiation at the proteome level. Our results contribute to the growing field of clinical microbial proteogenomics and can improve our understanding of phenotypic variation in clinical M. tuberculosis isolates.
引用
收藏
页码:3841 / 3851
页数:11
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