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

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Abstract

Lipids are most adaptable molecules that acclimatize to the development of multidrug resistance (MDR). The precise molecular mechanism of this acclimatization achieved in Mycobacterium tuberculosis (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.

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References

  • Bailo R, Bhatt A, Aínsa JA (2015) Lipid transport in Mycobacterium tuberculosis and its implications in virulence and drug development. Biochem Pharmacol 96:159–167

    Article  CAS  Google Scholar 

  • Camacho LR, Constant P, Raynaud C, Laneelle MA, Triccas JA, Gicquel B et al (2001) Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. J Biol Chem 276:19845–19854

    Article  CAS  Google Scholar 

  • Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509

    CAS  Google Scholar 

  • Forrellad MA, Klepp LI, Gioffré A, Sabio García J, Morbidoni HR, de la Paz Santangelo M, Cataldi AA, Bigi F (2013) Virulence factors of the Mycobacterium tuberculosis complex. Virulence 4(1):3–66

    Article  Google Scholar 

  • Gebhardt H, Meniche X, Tropis M, Krämer R, Daffé M, Morbach S (2007) The key role of the mycolic acid content in the functionality of the cell wall permeability barrier in Corynebacterineae. Microbiology 153:1424–1434

    Article  CAS  Google Scholar 

  • Guerin ME, Korduláková J, Alzari PM, Brennan PJ, Jackson M (2010) Molecular basis of phosphatidyl-myo-inositol mannoside biosynthesis and regulation in mycobacteria. J Biol Chem 285:33577–33583

    Article  CAS  Google Scholar 

  • Haites RE, Morita YS, McConville MJ, Billman-Jacobe H (2005) Function of phosphatidylinositol in mycobacteria. J Biol Chem 280:10981–10987

    Article  CAS  Google Scholar 

  • Jackson M (2014) The mycobacterial cell envelope-lipids. Cold Spring Harb Perspect Med 4(10):1–22

    Article  CAS  Google Scholar 

  • Jackson M, Crick DC, Brennan PJ (2000) Phosphatidylinositol is an essential phospholipid ofmycobacteria. J Biol Chem 275:30092–30099

    Article  CAS  Google Scholar 

  • Jain M, Petzold CJ, Schelle MW, Leavell MD, Mougous JD, Bertozzi CR et al (2007) Lipidomics reveals control of Mycobacterium tuberculosis virulence lipids via metabolic coupling. Proc Natl Acad Sci USA 104:5133–5138

    Article  CAS  Google Scholar 

  • Kovacevic S, Anderson D, Morita YS, Patterson J, Haites R, McMillan BN et al (2006) Identification of a novel protein with a role in lipoarabinomannan biosynthesis in mycobacteria. J Biol Chem 281:9011–9017

    Article  CAS  Google Scholar 

  • Kumar N, Kedarisetty CK, Kumar S, Khillan V, Sarin SK (2014) Antitubercular therapy in patients with cirrhosis: challenges and options. World J Gastroenterol 20:5760–5772

    Article  CAS  Google Scholar 

  • Lahiri N, Shah RR, Layre E, Young D, Ford C, Murray MB et al (2016) Rifampin resistance mutations are associated with broad chemical remodeling of Mycobacterium tuberculosis. J Biol Chem 291:14248–14256

    Article  CAS  Google Scholar 

  • Layre E, Al-Mubarak R, Belisle JT, Branch Moody D (2014) Mycobacterial lipidomics. Microbiol Spectr. doi:10.1128/microbiolspec

    Google Scholar 

  • Madigan CA, Martinot AJ, Wei JR, Madduri A, Cheng TY, Young DC et al (2015) Lipidomic analysis links mycobactin synthase K to iron uptake and virulence in M. tuberculosis. PLoS Pathog 11:e1004792

    Article  Google Scholar 

  • Mishra AK, Driessen NN, Appelmelk BJ, Besra GS (2011) Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol Rev 35:1126–1157

    Article  CAS  Google Scholar 

  • Pal R, Hameed S, Kumar P, Singh S, Fatima F (2015) Comparative lipidome profile of sensitive and resistant Mycobacterium tuberculosis strain. Int J Curr Microbiol Appl Sci. Special Issue 1:189–197

    Google Scholar 

  • Paul KC, Chu-Yuan L, Yasu SM (2013) Metabolism of plasma membrane lipids in Mycobacteria and Corynebacteria, lipid metabolism. In: Rodrigo Valenzuela Baez (ed) InTech. doi:10.5772/52781. https://www.intechopen.com/books/lipid-metabolism/metabolism-of-plasma-membranelipids-in-mycobacteria-and-corynebacteria

  • Rajni, Rao N, Meena LS (2011) Biosynthesis and virulent behavior of lipids produced by Mycobacterium tuberculosis: LAM and cord factor: an overview. Biotechnol Res Int 2011:274693

    Article  CAS  Google Scholar 

  • Ridell M, Wallerström G, Minnikin DE, Bolton RC, Magnusson M (1992) A comparative serological study of antigenic glycolipids from Mycobacterium tuberculosis. Tuber Lung Dis 73:101–105

    Article  CAS  Google Scholar 

  • Sabareesh V, Singh G (2013) Mass spectrometry based lipid(ome) analyzer and molecular platform: a new software to interpret and analyze electrospray and/or matrix-assisted laser desorption/ionization mass spectrometric data of lipids: a case study from Mycobacterium tuberculosis. J Mass Spectrom 48:465–477

    Article  CAS  Google Scholar 

  • Saini V, Farhana A, Steyn AJ (2012) Mycobacterium tuberculosis WhiB3: a novel iron-sulfur cluster protein that regulates redox homeostasis and virulence. Antioxid Redox Signal 16(7):687–697

    Article  CAS  Google Scholar 

  • Sartain MJ, Dick DL, Rithner CD, Crick DC, Belisle JT (2011) Lipidomic analyses of Mycobacterium tuberculosis based on accurate mass measurements and the novel “Mtb LipidDB. J Lipid Res 52:861–872

    Article  CAS  Google Scholar 

  • Shaw DJ, Robb K, Vetter BV, Tong M, Molle V, Hunt NT, Hoskisson PA (2017) Disruption of key NADH-binding pocket residues of the Mycobacterium tuberculosis InhA affects DD-CoA binding ability. Sci Rep 7(1):4714

    Article  Google Scholar 

  • Sinsimer D, Huet G, Manca C, Tsenova L, Koo MS, Kurepina N et al (2008) The phenolic glycolipid of Mycobacterium tuberculosis differentially modulates the early host cytokineresponse but does not in itself confer hypervirulence. Infect Immun 76:3027–3036

    Article  CAS  Google Scholar 

  • Slayden RA, Barry CE 3rd (2001) Analysis of the lipids of Mycobacterium tuberculosis. Methods Mol Med 54:229–245

    CAS  Google Scholar 

  • Syal K, Maiti K, Naresh K, Avaji PG, Chatterji D, Jayaraman N (2016) Synthetic arabinomannan glycolipids impede mycobacterial growth, sliding motility and biofilm structure. Glycoconj J 33:763–777

    Article  CAS  Google Scholar 

  • Velayati AA, Farnia P, Ibrahim TA, Haroun RZ, Kuan HO, Ghanavi J et al (2009) Differences in cell wall thickness between resistant and nonresistant strains of Mycobacterium tuberculosis: using transmission electron microscopy. Chemotherapy 55(5):303–307

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Dr. Sanjeev Kanojiya, Central Drug Research Institute (CDRI), Lucknow for assisting us in mass spectrometry experiments. We thank Dr. V. Sabareesh for his intellectual support in data analysis.

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Correspondence to Zeeshan Fatima.

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The authors declare that they have no competing interests.

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Z.F. thanks Science and Engineering Research Board (SERB), New Delhi (SR/FT/LS-173/2010) for the financial assistance in the form of Young Scientist award.

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Pal, R., Hameed, S., Kumar, P. et al. Comparative lipidomics of drug sensitive and resistant Mycobacterium tuberculosis reveals altered lipid imprints. 3 Biotech 7, 325 (2017). https://doi.org/10.1007/s13205-017-0972-6

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