Lineage-Specific Proteomic Signatures in the Mycobacterium Tuberculosis Complex Reveal Differential Abundance of Proteins Involved in Virulence, DNA Repair, CRISPR-Cas, Bioenergetics and Lipid Metabolism

ABSTRACT: Despite the discovery of Mycobacterium tuberculosis (Mtb) more than 130 years ago, Mtb physiology and the mechanisms of virulence are still not fully understood. The objective of this study was to compare and characterize the differentially abundant protein profiles of modern, pre-modern and ancient Mtb lineages. Using a comprehensive analysis of the proteome of Mtb lineages 3, 4, 5 and 7, unique and shared proteomic signatures in these modern, pre-modern and ancient Mtb lineages were delineated. Main proteomic findings were verified by using immunoblotting. In addition, analysis of multiple genome alignment of all lineages was performed using Geneious Prime software. Label-free peptide quantification of whole cells from Mtb lineage 3, 4, 5 and 7 yielded 38,346 unique peptides derived from 3092 proteins, representing 77% coverage of the predicted Mtb proteome. Mtb lineage-specific differential abundances was observed for 539 proteins. Lineage 7 exhibited a markedly reduced abundance of proteins involved in DNA repair, type VII ESX-3 and ESX-1 secretion systems, lipid metabolism and inorganic phosphate uptake, and an increased abundance of proteins involved in alternative pathways of the TCA cycle and the CRISPR/Cas system as compared to the other lineages. Lineages 3 and 4 exhibited a higher abundance of proteins involved in virulence, DNA repair, drug resistance and other metabolic pathways. The high throughput analysis of Mtb proteome by super resolution massspectrometry provided an insight into the differential expression of proteins between Mtb lineages 3, 4, 5 and 7 that may explain the slow growth and reduced virulence of lineage 7, as well as metabolic flexibility and the ability to survive under adverse growth conditions.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mycobacterium Tuberculosis

TISSUE(S): Cell Culture

DISEASE(S): Tuberculosis

SUBMITTER: Tahira Riaz  

LAB HEAD: Tone Tønjum

PROVIDER: PXD020383 | Pride | 2020-09-01

REPOSITORIES: Pride