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Molecules 2015, 20(2), 2775-2785;

The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides

Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK
School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, Stockton-on-Tees TS17 6BH, UK
Authors to whom correspondence should be addressed.
Academic Editor: Thomas J. Schmidt
Received: 11 December 2014 / Accepted: 28 January 2015 / Published: 6 February 2015
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Natural product antimicrobial peptides (AMPs) have been proposed as promising agents against the Leishmania species, insect vector borne protozoan parasites causing the neglected tropical disease leishmaniasis. However, recent studies have shown that the mammalian pathogenic amastigote form of L. mexicana, a causative agent of cutaneous leishmaniasis, is resistant to the amphibian-derived temporin family of AMPs when compared to the insect stage promastigote form. The mode of resistance is unknown, however the insect and mammalian stages of Leishmania possess radically different cell surface coats, with amastigotes displaying low (or zero) quantities of lipophosphoglycan (LPG) and proteophosphoglycan (PPG), macromolecules which form thick a glycocalyx in promastigotes. It has been predicted that negatively charged LPG and PPG influence the sensitivity/resistance of promastigote forms to cationic temporins. Using LPG and PPG mutant L. mexicana, and an extended range of temporins, in this study we demonstrated that whilst LPG has little role, PPG is a major factor in promastigote sensitivity to the temporin family of AMPs, possibly due to the conferred anionic charge. Therefore, the lack of PPG seen on the surface of pathogenic amastigote L. mexicana may be implicated in their resistance to these peptides. View Full-Text
Keywords: Leishmania mexicana; cutaneous leishmaniasis; drug therapy; antimicrobial peptide Leishmania mexicana; cutaneous leishmaniasis; drug therapy; antimicrobial peptide

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Eggimann, G.A.; Sweeney, K.; Bolt, H.L.; Rozatian, N.; Cobb, S.L.; Denny, P.W. The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides. Molecules 2015, 20, 2775-2785.

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