Lipidomics and genomics of Mycobacterium tuberculosis reveal lineage-specific trends in mycolic acid biosynthesis.
Bottom Line: We found significant variations in the MA patterns between different MTBC strains and lineages.By interrogating the whole genome sequences of these MTBC strains, we identified relevant single-nucleotide polymorphisms that may sustain the lineage-specific MA patterns.Our results show that the strain genetic background influences MA metabolism and suggests that strain diversity should be considered in the development of new anti-tuberculosis drugs that target MA synthesis.
Affiliation: Mycobacterial Division Research, NIMR, MRC, NW71AA, London, United Kingdom; Department of Medical Parasitology and Infection Biology, Swiss TPH, 4002, Basel, Switzerland; University of Basel, 4002, Basel, Switzerland.Show MeSH
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Mentions: A principal component analysis based on median-fold normalized intensities of the MA species accounted for 99.5% of variance within the first two components. As depicted in Figure 4D, Lineage 1 and Lineage 6 strains formed independent clusters, whereas strains belonging to the “modern” lineages were indistinguishable from each other (Fig. 4D). Hence, Lineage 2 and 4 strains were subsequently grouped as “modern” for statistical comparisons with strains from Lineages 1 and 6. Relative intensity plots revealed that alpha-MAs in Lineage 6 and methoxy-MAs in Lineage 1 strains were statistically significantly less-represented in comparison with the other lineages (Fig. 5A). Computing the ratios between methoxy- and keto-MAs revealed a statistically significant inversion in Lineage 1 (median: 0.87) as compared with the “modern” lineages (median: 1.06, P = 0.004) and Lineage 6 (median: 1.36, P = 0.009) (Fig. 5B). Similarly, we calculated the ratios between oxygenated-MAs (methoxy + keto) and alpha-MAs and found a statistically significant increase for Lineage 6 (median: 1.44) compared with the “modern” lineages (median: 1.266, P = 0.017) and Lineage 1 strains (median: 1.118, P = 0.02) (Fig. 5B).
Affiliation: Mycobacterial Division Research, NIMR, MRC, NW71AA, London, United Kingdom; Department of Medical Parasitology and Infection Biology, Swiss TPH, 4002, Basel, Switzerland; University of Basel, 4002, Basel, Switzerland.