Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates

Handle URI:
http://hdl.handle.net/10754/625389
Title:
Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates
Authors:
Heunis, Tiaan; Dippenaar, Anzaan; Warren, Robin M.; van Helden, Paul D.; van der Merwe, Ruben G.; Gey van Pittius, Nicolaas C.; Pain, Arnab ( 0000-0002-1755-2819 ) ; Sampson, Samantha L.; Tabb, David L.
Abstract:
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 utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome 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 ~9% of all total 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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Pathogen Genomics Laboratory
Citation:
Heunis T, Dippenaar A, Warren RM, van Helden PD, van der Merwe RG, et al. (2017) Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates. Journal of Proteome Research. Available: http://dx.doi.org/10.1021/acs.jproteome.7b00483.
Publisher:
American Chemical Society (ACS)
Journal:
Journal of Proteome Research
Issue Date:
18-Aug-2017
DOI:
10.1021/acs.jproteome.7b00483
Type:
Article
ISSN:
1535-3893; 1535-3907
Sponsors:
This work was supported by the South African National Research Foundation (NRF), South African Medical Research Council (SAMRC), Harry Crossley Foundation, Claude Leon Foundation, the Department of Biomedical Sciences, Stellenbosch University and King Abdullah University of Science and Technology (KAUST award number BAS/1/1020-01-01). S.L. Sampson is funded by the South African Research Chairs Initiative of the Department of Science and Technology and NRF of South Africa, award number UID 86539. D.L. Tabb is funded by the SAMRC under the South African Tuberculosis Bioinformatics Initiative.
Additional Links:
http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.7b00483
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorHeunis, Tiaanen
dc.contributor.authorDippenaar, Anzaanen
dc.contributor.authorWarren, Robin M.en
dc.contributor.authorvan Helden, Paul D.en
dc.contributor.authorvan der Merwe, Ruben G.en
dc.contributor.authorGey van Pittius, Nicolaas C.en
dc.contributor.authorPain, Arnaben
dc.contributor.authorSampson, Samantha L.en
dc.contributor.authorTabb, David L.en
dc.date.accessioned2017-08-23T11:54:06Z-
dc.date.available2017-08-23T11:54:06Z-
dc.date.issued2017-08-18en
dc.identifier.citationHeunis T, Dippenaar A, Warren RM, van Helden PD, van der Merwe RG, et al. (2017) Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates. Journal of Proteome Research. Available: http://dx.doi.org/10.1021/acs.jproteome.7b00483.en
dc.identifier.issn1535-3893en
dc.identifier.issn1535-3907en
dc.identifier.doi10.1021/acs.jproteome.7b00483en
dc.identifier.urihttp://hdl.handle.net/10754/625389-
dc.description.abstractMycobacterium 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 utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome 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 ~9% of all total 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.en
dc.description.sponsorshipThis work was supported by the South African National Research Foundation (NRF), South African Medical Research Council (SAMRC), Harry Crossley Foundation, Claude Leon Foundation, the Department of Biomedical Sciences, Stellenbosch University and King Abdullah University of Science and Technology (KAUST award number BAS/1/1020-01-01). S.L. Sampson is funded by the South African Research Chairs Initiative of the Department of Science and Technology and NRF of South Africa, award number UID 86539. D.L. Tabb is funded by the SAMRC under the South African Tuberculosis Bioinformatics Initiative.en
dc.publisherAmerican Chemical Society (ACS)en
dc.relation.urlhttp://pubs.acs.org/doi/abs/10.1021/acs.jproteome.7b00483en
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.7b00483.en
dc.subjectMycobacterium tuberculosisen
dc.subjectclinical microbial proteogenomicsen
dc.subjectvariant peptidesen
dc.subjectstrain variationen
dc.titleProteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolatesen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentPathogen Genomics Laboratoryen
dc.identifier.journalJournal of Proteome Researchen
dc.eprint.versionPost-printen
dc.contributor.institutionDST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africaen
kaust.authorPain, Arnaben
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