Abstract
Mycobacterium has evolved distinct cell wall and strategies such as biofilm formation, which helps it to survive in hostile conditions. We have reported previously that arabinofuranoside containing glycolipids exhibit inhibition activities against the above functions of the mycobacterial species M. smegmatis. In search for activities mediated by oligosaccharide glycolipids, we report herein the inhibitory activities of a linear and a branched pentasaccharides having arabinan and mannan moieties. In the presence of the pentasaccharide glycolipids, a significant reduction in mycobacterial growth is observed, concomitant with reductions in sliding motility and colonization through biofilm formation, at the optimal glycolipid concentrations of 50–100 μg mL−1. Especially the biofilm coat is ruptured by ~80–85 % in the presence of glycolipids. Pentasaccharides alone without the lipidic chain show only a weak effect. The glycolipids are non-toxic, as evaluated through their effect on RBCs. Analysis of the mycolic acid profile of glycolipid treated biofilm shows that α- and epoxy mycolic acids are downregulated significantly, in comparison to glycolipid untreated biofilms. Lipidomics profile analysis through mass spectrometry further reveals profound downregulation of phosphatidylinositol mannosides, acylatedphosphoglycerols and mycolic acid family, namely, keto-, alpha- and methoxymycolic acids.
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Abbreviations
- LAM:
-
Lipoarabinomannan
- ESI:
-
Electrospray ionization
- RBC:
-
Red blood cells
- GPL:
-
Glycopeptidolipids
- GL:
-
Glycolipids
- O.D.:
-
Optical density
- PBS:
-
Phosphate-buffered saline
- SDS:
-
Sodium dodecyl sulphate
- FAME:
-
Fatty acid methyl ester
- MAME:
-
Mycolic acid methyl ester
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Acknowledgment
We are grateful to the Department of Science and Technology, New Delhi, for a financial support of this work. Council of Scientific and Industrial Research, New Delhi, is acknowledged for a research fellowship to KS and KGM. We thank Rajesh from Brukers and Sunita from Proteomics Facility, IISc, for help in the analysis of lipids.
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Syal, K., Maiti, K., Naresh, K. et al. Synthetic arabinomannan glycolipids impede mycobacterial growth, sliding motility and biofilm structure. Glycoconj J 33, 763–777 (2016). https://doi.org/10.1007/s10719-016-9670-6
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DOI: https://doi.org/10.1007/s10719-016-9670-6