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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.

frontiers in microbiology

Comparative Proteomic Analysis of Mycobacterium tuberculosis Lineage 7 and Lineage 4 Strains Reveals Differentially Abundant Proteins Linked to Slow Growth and Virulence