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

被引:26
作者
Eggimann, Gabriela A. [1 ,2 ]
Sweeney, Kathryn [1 ,2 ]
Bolt, Hannah L. [1 ,2 ]
Rozatian, Neshat [1 ,2 ]
Cobb, Steven L. [1 ,2 ]
Denny, Paul W. [1 ,2 ,3 ]
机构
[1] Univ Durham, Biophys Sci Inst, Dept Chem, Durham DH1 3LE, England
[2] Univ Durham, Sch Biol & Biomed Sci, Durham DH1 3LE, England
[3] Univ Durham, Sch Med Pharm & Hlth, Stockton On Tees TS17 6BH, England
基金
瑞士国家科学基金会; 英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
AMPHOTERICIN-B; VISCERAL LEISHMANIASIS; LIPOPHOSPHOGLYCAN; RESISTANCE; PROTEOPHOSPHOGLYCAN; PROMASTIGOTES; AMASTIGOTES; MACROPHAGES; DEFICIENT; PARASITES;
D O I
10.3390/molecules20022775
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2775 / 2785
页数:11
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