Comparative lipidomics of drug sensitive and resistant Mycobacterium tuberculosis reveals altered lipid imprints

Abstract

Lipids are most adaptable molecules that acclimatize to the development of multidrug resistance (MDR). The precise molecular mechanism of this acclimatization achieved in (MTB) remains elusive. Although lipids of MTB have been characterized to some details, a comparable resource does not exist between drug sensitive (DS) and resistant (DR) strains of MTB. Here, by employing high-throughput mass spectrometry-based lipidomic approach, we attempted to analyze the differential lipidome profile of DS and DR MTB clinical isolates. We analyzed three major classes of lipids viz fatty acyls, glycerophospholipids and glycerolipids and their respective subclasses. Notably, we observed differential fatty acyls and glycerophospholipids as evident from increased mycolic acids phosphatidylinositol mannosides, phosphatidylinositol, cardiolipin and triacylglycerides abundance, respectively, which are crucial for MTB virulence and pathogenicity. Considering the fact that 30% of the MTB genome codes for lipid, this comprehensive lipidomic approach unravels extensive lipid alterations in DS and DR that will serve as a resource for identifying biomarkers aimed at disrupting the functions of MTB lipids responsible for MDR acquisition in MTB.

Investigations into Isoniazid TreatedMycobacterium tuberculosisby Electrospray Mass Spectrometry Reveals New Insights into Its Lipid Composition

“…When MTB bacilli are in dormant stage or stress condition they accumulate TGs. When MTB requires energy, the TGs are catabolized by lipase enzymes that are present on the outer wall to generate FAs that could be used for energy production [ 21 , 27 ]. Herein, we found that the lipase activity was significantly decreased in the presence of INH ( Figure 4 ), which means low burning and less utilization of accumulated TGs that are required by the MTB under stress conditions, such as presence of INH in this case [ 35 ].…”

“…Cells of MTB untreated (control) and INH treated at exponential phase were used for whole cell lipid extraction by modified Folch method [ 21 , 23 ]. Briefly, the MTB treated and untreated cells were harvested at 10,000 rpm for 10 minutes.…”

“…Lipid biology has evolved to a greater extent during the last decade, primarily attributed to advancements in the sophistication of mass spectrometry (MS) instrumentation [ 12 , 13 ]. Many studies have noted altered lipid metabolism associated with diseases including TB [ 14 – 21 ]. Therefore, study of lipid profiles by high-throughput lipidomics approach involving MS has gained significant importance in recent times.…”

Pediatric Tuberculosis: The Impact of “Omics” on Diagnostics Development

“…More than 40 of these mycobacterial lipids lack any similarity to other eukaryotic or Gram-negative organisms, making them unique signatures for diagnostics development and therapeutic targeting. The unique Mycobacterial lipidome is, thus, a signature repository that requires further characterization [ 112 ]. When comparing the lipid profile from normally grown MTB with dormant and reactivated bacteria, analysis revealed a total of 4187 significant features with 2480 features found to have significant variation during the transition from normoxial growth to dormancy.…”

Elucidating the Mechanism of Vanillin Induced Mycobacterial Membrane Disruption: Implications of Lipid Alteration

“…Untreated (control) and Van treated cells of M. smegmatis at exponential phase were used for lipid extraction by Folch method with slight modification [12]. Briefly, the cells were harvested at 10,000 rpm for 10 min.…”