title: Lipid composition is an important determinant of antimicrobial activity of alpha-melanocyte stimulating hormone.
abstract: We have reported strong antimicrobial activity of cationic neuropeptide α-MSH against Staphylococcus aureus. Clinical S. aureus isolates non-susceptible to the peptide had higher amount of cationic phospholipid. To elucidate the molecular basis of lipid selectivity and antimicrobial activity of α-MSH, studies were carried out on SUVs having different combinations of neutral DMPC and anionic lipids DMPG to mimic mammalian and bacterial membrane. The peptide interacted with the DMPG containing vesicles only, as evident from the changes in Trp fluorescence. CD spectroscopy revealed that despite interaction, the peptide retained its native random coil structure. The perturbation of the vesicles caused by peptide interaction is strongly dependent on peptide concentration as seen both by DLS and Tb(3+)/DPA based fluorescence leakage assay. Our data clearly demonstrate the preference of α-MSH to interact with anionic DMPG containing vesicles leading to significant permeabilization which is the molecular basis behind the selectivity of α-MSH for bacterial systems.
authors.affiliation: School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Tahsina
authors.initials: T
authors.lastname: Shireen
authors.affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics 1/AF, Bidhannagar, Kolkata 700064, India.
authors.forename: Arnab
authors.initials: A
authors.lastname: Basu
authors.affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics 1/AF, Bidhannagar, Kolkata 700064, India.
authors.forename: Munna
authors.initials: M
authors.lastname: Sarkar
authors.affiliation: School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: kasturim@mail.jnu.ac.in.
authors.forename: Kasturi
authors.initials: K
authors.lastname: Mukhopadhyay
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D006801:Humans; D008027:Light; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D000521:alpha-MSH / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D008081:Liposomes; D010715:Phosphatidylglycerols; D000521:alpha-MSH; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine
keywords: Antimicrobial peptide; Circular dichroism spectroscopy; Dynamic light scattering; Membrane permeabilization; Peptide-membrane interaction; Trp-fluorescence