4.6 Article

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

Journal

MOLECULES
Volume 20, Issue 2, Pages 2775-2785

Publisher

MDPI
DOI: 10.3390/molecules20022775

Keywords

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Funding

  1. asdf
  2. Wolfson Research Institute Small Grants Award
  3. BBSRC Sparking Impact Award
  4. Ramsay Memorial Trust Fellowship
  5. Royal Society [RG090808]
  6. Swiss National Science Foundation Fellowship
  7. HLB by an Engineering and Physical Sciences Research Council UK Studentship
  8. Engineering and Physical Sciences Research Council [1342926] Funding Source: researchfish

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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.

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