Comparative Proteomic Analysis of the Mycobacterium tuberculosis Lineage 7 Reveals Differentially Abundant Proteins Linked to Slow Growth

Differentially abundant proteins were quantified in the slowly growing Mycobacterium tuberculosis (M. tuberculosis) lineage 7 strains and the M. tuberculosis lineage 4 reference strain H37Rv. Mass spectrometry based proteomic analysis was employed to identify, quantitate and compare the protein profiles of strains from the two M. tuberculosis lineages (lineage 7 and 4). Label-free peptide quantification of whole cells from M. tuberculosis lineage 7 and 4 yielded the identification of 2825 and 2541 proteins, respectively. A combined total of 2867 protein groups covering 71% of the predicted M. tuberculosis proteome were identified. Comparative proteomic mapping of M. tuberculosis lineage 7 and 4 strains showed that the abundance of 125 proteins was significantly altered. Functional analysis showed that a number of M. tuberculosis proteins involved in growth and virulence were less abundant in lineage 7 compared to lineage 4. Five ABC transporter proteins, three phosphate binding proteins essential for inorganic phosphate uptake, and six components of the type 7 secretion system ESX-3 involved in iron acquisition were less abundant in M. tuberculosis lineage 7. This proteogenomic analysis provided an insight into the lineage 7-specific protein profile which may provide cues to understanding the differential properties of lineage 7 strains in terms of slow growth, survival fitness and pathogenesis.