Synthetic arabinomannan glycolipids impede mycobacterial growth, sliding motility and biofilm structure.
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.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, India.
Kirtimaan
K
Syal
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
Krishnagopal
K
Maiti
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
Kottari
K
Naresh
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.
Prakash Gouda
PG
Avaji
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, India. dipankar@mbu.iisc.ernet.in.
Dipankar
D
Chatterji
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India. jayaraman@orgchem.iisc.ernet.in.
Narayanaswamy
N
Jayaraman
D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D006017:Glycolipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008351:Mannans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020102:Mycobacterium smegmatis / Q000502:physiology*
D006017:Glycolipids; D008351:Mannans; C012189:arabinomannan
Biofilms; Glycolipids; Mycobacteria; Oligosaccharides; Sliding motility