In order to decipher the nature of the slowly growing Mycobacterium tuberculosis (M.
tuberculosis) lineage 7, the differentially abundant
proteins in strains of M.
tuberculosis lineage 7 and lineage 4 were defined. Comparative proteomic analysis by mass spectrometry was employed to identify, quantitate and compare the
protein profiles of strains from the two M.
tuberculosis lineages. 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. The abundance of 125
proteins in M.
tuberculosis lineage 7 and 4 strains was significantly altered. Notably, the analysis showed that a number of M.
tuberculosis proteins involved in growth and virulence were less abundant in lineage 7 strains 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 clues to understanding the differential properties of lineage 7 strains in terms of slow growth, survival fitness, and pathogenesis.