201. Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosisIsolates
- Author
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Heunis, Tiaan, Dippenaar, Anzaan, Warren, Robin M., van Helden, Paul D., van der Merwe, Ruben G., Gey van Pittius, Nicolaas C., Pain, Arnab, Sampson, Samantha L., and Tabb, David L.
- Abstract
Mycobacterium tuberculosisconsists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosisisolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of the utmost importance to fully understand M. tuberculosisbiology 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. tuberculosisLatin American-Mediterranean isolates. Using this approach, we identified 59 peptides containing single amino acid variants, which covered ∼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. tuberculosisH37Rv reference proteome. Here, we provide evidence for the expression of this protein in the clinical M. tuberculosisSAWC3651 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. tuberculosisisolates 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. tuberculosisisolates.
- Published
- 2024
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