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

Abstract

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.

PPE37 Is Essential for Mycobacterium tuberculosis Heme-Iron Acquisition (HIA), and a Defective PPE37 in Mycobacterium bovis BCG Prevents HIA

“…The ppe37 genes of M. tuberculosis, virulent M. bovis, and BCG are all transcribed at relatively low levels (when not induced by low iron), but PPE37 is often not detected by proteomics methods even with high coverage of the theoretical proteome, likely due to low expression and the general difficulty in detecting acidic PE/PPE proteins (45)(46)(47)(48)(49). However, one study which achieved 87% coverage of the BCG proteome by separately analyzing cell wall, plasma membrane, and cytoplasm fractions identified PPE37, indicating that the protein is expressed by BCG (50).…”

Molecular epidemiology of clinical Mycobacterium tuberculosis complex isolates in South Omo, Southern Ethiopia

“…Understanding the molecular epidemiology of TB is important for regional disease control. For instance, distinct strains may be linked to outbreaks [10], high virulence [42], emergency of drug resistance [44], disease progression [43], and can point to the geographic origin of a strain [20,33] as well as identify new lineages [17,28].…”

Nε- and O-Acetylation in Mycobacterium tuberculosis Lineage 7 and Lineage 4 Strains: Proteins Involved in Bioenergetics, Virulence, and Antimicrobial Resistance Are Acetylated

“…Lineage 7 is a recently identified lineage of Mtb, characterized by slow-growth and reduced virulence phenotypes. 100,101 The GO enrichment analysis of 161 proteins hypoacetylated in lineage 7 revealed that pathogenesis, growth, glycolysis, response to iron ion, response to nitrosative stress, and protein folding were among the significantly enriched biological processes (Figure 7A,B). Carbon metabolism, TCA cycle, oxidative phosphorylation, and microbial metabolism in diverse environments were some of the significantly enriched pathways from these hypoacetylated proteins (Figure 7B, Table S6-2).…”