Lipidomic insights to understand membrane dynamics in response to vanillin in Mycobacterium smegmatis
Considering the emergence of multidrug resistance (MDR) in prevalent human pathogen, Mycobacterium tuberculosis (MTB), there is parallel spurt in development of novel strategies aimed to disrupt MDR. The cell envelope of MTB comprises a wealth of lipid moieties contributing towards long-term survival of pathogen that could be exploited as efficient antitubercular target owing to advancements made in mass spectrometry–based lipidomics technology. This study aimed to utilize the lipidomics approach to unveil several lipid associated changes in response to natural antimycobacterial compound vanillin (Van) in Mycobacterium smegmatis, a surrogate for MTB. Lipidomic analyses revealed that that Van alters the composition of fatty acid (FA), glycerolipid (GL), glycerophospholipid (GP), and saccharolipids (SL). Furthermore, Van leads to potentiation of ampicillin and displayed additive effect. The differential expressions of various lipid biosynthetic pathway genes by RT-PCR corroborated with the lipidomics data. Lastly, we demonstrated enhanced survival of Mycobacterium-infected Caenorhabditis elegans model in presence of Van. Thus, lipidomics approach provided detailed insight into mechanisms of membrane disruption by Van in Mycobacterium smegmatis. Our work offers the basis of further understanding the regulation of lipid homeostasis in MTB so that better therapeutic targets could be identified to combat MDR.
KeywordsMycobacterium Vanillin Lipids Cell wall Fatty acid Glycerolipids Glycerophospholipids
We thank Anindya Ghosh for providing wild-type C. elegans (N2) and Escherichia coli OP50 strains as generous gift. We are grateful to Sarman Singh and Pramod Mehta for providing M. smegmatis and M. marinum strains as generous gifts, respectively. We thank Sanjeev Kanojiya for assisting us in mass spectrometry experiments. We thank Varatharajan Sabareesh for his intellectual support in lipidome data analysis.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Brenner S (1974) The genetics of Caenorhabditis elegans. Genetic 77:71–94Google Scholar
- Grzegorzewicz AE, Pham H, Gundi VA, Scherman MS, North EJ, Hess T, Jones V, Gruppo V, Born SE, Korduláková J, Chavadi SS, Morisseau C, Lenaerts AJ, Lee RE, McNeil MR, Jackson M (2012) Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat Chem Biol 8:334–341CrossRefPubMedPubMedCentralGoogle Scholar
- Layre E, Sweet L, Hong S, Madigan CA, Desjardins D, Young DC, Cheng TY, Annand JW, Kim K, Shamputa IC, McConnell MJ, Debono CA, Behar SM, Minnaard AJ, Murray M, Barry CE, Matsunaga I, Moody DB (2011) A comparative lipidomics platform for chemotaxonomic analysis of Mycobacterium tuberculosis. Chem Biol 18:1537–1549CrossRefPubMedPubMedCentralGoogle Scholar
- Nass R, Hamza I (2007) The nematode C. elegans as an animal model to explore toxicology in vivo: solid and axenic growth culture conditions and compound exposure parameters. Curr Protoc Toxicol chapter 1: Unit1 9. https://doi.org/10.1002/0471140856.tx0109s31.
- National Committee for Clinical and Laboratory Standards (2008) Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, vol. 28, no. 14, Approved standard M27-A3. National Committee for Clinical and Laboratory Standards, Wayne, Ill, USAGoogle Scholar
- Pal R, Hameed S, Kumar P, Singh S, Fatima Z (2015) Comparative lipidome profile of sensitive and resistant Mycobacterium tuberculosis strain. Int J Curr Microbiol App Sci 2015:189–197Google Scholar
- Pal R, Hameed S, Fatima Z (2017) Lipidomics: novel strategy to conquer antimicrobial resistance. Antimicrobial Research: Novel bioknowledge and educational programs. (Microbiology Book Series, number # 6). Formatex Research Center, Spain. Ed: A. Mendez-Vilas. pp: 644–650.Google Scholar
- Rodríguez JE, Ramírez AS, Salas LP, Helguera-Repetto C, Gonzalez-y-Merchand J, Soto CY, Hernández-Pando R (2013) Transcription of genes involved in sulfolipid and polyacyltrehalose biosynthesis of Mycobacterium tuberculosis in experimental latent tuberculosis infection. PLoS One 8:e58378CrossRefPubMedPubMedCentralGoogle 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 48:465–477CrossRefPubMedGoogle Scholar
- Sharma S, Hans S, Hameed S, Fatima Z (2017) Elucidating the mechanism of vanillin induced mycobacterial membrane disruption: implications of lipid alterations. SOJ Microbiol Infect Dis 5:1–7Google Scholar
- Sharma S, Hameed S, Fatima Z (2018) Mycobacterial lipids as potential drug target to combat tuberculosis, “Understanding microbial pathogens: current knowledge and educational ideas on antimicrobial research” Microbiology Book Series 7. Formatex Research Center, Spain. Ed: A. Mendez-Vilas. Pp: 200–207.Google Scholar
- Škovierová H, Larrouy-Maumus G, Zhang J, Kaur D, Barilone N, Korduláková J, Gilleron M, Guadagnini S, Belanová M, Prevost MC, Gicquel B, Puzo G, Chatterjee D, Brennan PJ, Nigou J, Jackson M (2009) AftD, a novel essential arabinofuranosyltransferase from mycobacteria. Glycobiology 19:1235–1247CrossRefPubMedPubMedCentralGoogle Scholar