title: The role of phosphoglycans in the susceptibility of Leishmania mexicana to the temporin family of anti-microbial peptides.
abstract: 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.
authors: Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK. gabriela.eggimann@durham.ac.uk.
authors: Gabriela A
authors: GA
authors: Eggimann
authors: Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK. kathrynsweeney@hotmail.com.
authors: Kathryn
authors: K
authors: Sweeney
authors: Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK. h.l.bolt@durham.ac.uk.
authors: Hannah L
authors: HL
authors: Bolt
authors: Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK. neshat.rozatian@durham.ac.uk.
authors: Neshat
authors: N
authors: Rozatian
authors: Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK. s.l.cobb@durham.ac.uk.
authors: Steven L
authors: SL
authors: Cobb
authors: Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK. p.w.denny@durham.ac.uk.|School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, Stockton-on-Tees TS17 6BH, UK. p.w.denny@durham.ac.uk.
authors: Paul W
authors: PW
authors: Denny
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007894:Leishmania mexicana / Q000254:growth & development*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D011134:Polysaccharides; D011506:Proteins; C104501:temporin