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Published on: March 6, 2019
Lipid composition is an important determinant of antimicrobial activity of alpha-melanocyte stimulating hormone
Tahsina Shireen1, Arnab Basu2, Munna Sarkar2
1School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
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.
Insights
The neuropeptide alpha-MSH selectively targets bacterial membranes due to their anionic lipid content. This interaction causes membrane permeabilization, explaining its antimicrobial activity against bacteria like Staphylococcus aureus.
Area of Science:
- Biochemistry
- Microbiology
- Molecular Biology
Background:
- Cationic neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) exhibits antimicrobial activity against Staphylococcus aureus.
- Bacterial isolates resistant to α-MSH show increased levels of cationic phospholipids.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the lipid selectivity and antimicrobial action of α-MSH.
- To elucidate how α-MSH interacts with membranes of varying lipid compositions.
Main Methods:
- Utilized small unilamellar vesicles (SUVs) composed of neutral (DMPC) and anionic (DMPG) lipids to model bacterial and mammalian membranes.
- Employed tryptophan fluorescence, circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and a terbium/dipicolinic acid (Tb(3+)/DPA) fluorescence leakage assay.
Main Results:
- α-MSH selectively interacted with DMPG-containing vesicles, indicating a preference for anionic lipids.
- CD spectroscopy confirmed that α-MSH maintained its random coil structure upon interaction.
- Peptide concentration-dependently perturbed vesicles, leading to significant membrane permeabilization, as observed by DLS and fluorescence leakage.
Conclusions:
- α-MSH demonstrates a clear preference for anionic lipids, characteristic of bacterial membranes.
- This lipid selectivity and subsequent membrane permeabilization are the molecular basis for α-MSH's antimicrobial efficacy against bacterial systems.
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