Leishmania-sand fly interactions controlling species-specific vector competence. Microreview

Abstract

Leishmaniasis is caused by a wide range of parasites that are transmitted by an even wider range of sand fly vectors. The phlebotomine vectors of Leishmaniasis are in some cases only permissive to the complete development of the species of Leishmania that they transmit in nature. The parasite–sand fly interactions that control this specificity are related to differences in the ability of the parasite to inhibit or to resist killing by proteolytic enzymes released into the mid‐gut soon after blood feeding, and/or to maintain infection in the mid‐gut during excretion of the digested blood meal. In each case, surface expressed or released phosphoglycan‐containing molecules appear to promote parasite survival. The evidence that the surface lipophosphoglycan (LPG) mediates promastigote attachment to the mid‐gut epithelium so as to prevent their loss during blood‐meal excretion is especially strong based on the comparison of development in sand flies using LPG‐deficient mutants. LPG displays interspecies polymorphisms in their phosphoglycan domains that in most cases can fully account for species‐specific vector competence.

Therapeutic Efficacy Evaluation of Metronidazole and Some Antifungal Agents with Meglumine Antimoniate on Visceral Leishmaniasis by Real-Time Light-Cycler (LC) PCR in BALB/c Mice

“…Two million new human cases arise every year, and at least 350 million peoples are exposed to the risk of Leishmania parasite infection [3]. Experimental hosts, such as laboratory mice, are largely used to study the immunobiology of these parasites and to screen the efficacy of newly developed drugs and vaccines [4]. Most of those studies require detection and quantitation of the Leishmania burdens in different mouse tissues.…”

Two Functionally Divergent UDP-Gal Nucleotide Sugar Transporters Participate in Phosphoglycan Synthesis in Leishmania major

“…PG repeats frequently contain additional sugar substitutions in different species and strains, most commonly on the Gal residue, although modifications of the Man also occur ( Fig. 1) (6).…”

Functional Identification of Galactosyltransferases (SCGs) Required for Species-specific Modifications of the Lipophosphoglycan Adhesin Controlling Leishmania major-Sand Fly Interactions

“…Several studies have emphasized the importance of lipophosphoglycan (LPG), 1 an abundant surface glycolipid of Leishmania promastigotes, in sand fly survival (reviewed in Refs. [2][3][4]. Following a sand fly bite, Leishmania and the blood meal are enclosed by a midgut peritrophic matrix for several days, whereas parasites differentiate to the replicating procyclic promastigote stage.…”

“…In different species and/or developmental stages a variety of modifications of the LPG backbone have been observed, including changes in the terminal capping oligosaccharide of LPG, the addition of side chain (sc) sugar modifications to the prototypic PG (Gal-Man-P) repeating unit, and increases in the number of PG repeats (reviewed in Refs. [2][3][4]. These modifications contribute in a species-specific manner to the binding and release of Leishmania promastigotes during development in the sand fly.…”

“…In L. major the PG repeats are modified by side chain ␤1,3 galactosyl residues (sc␤Gal); in metacyclics, the number of PG repeats increases and the sc␤Gal residues are further modified by addition of arabinose caps to block midgut binding (6,7). These species-specific modifications also play important roles in the ability of the natural sand fly vector to transmit Leishmania species (2)(3)(4). For example, neither L. donovani nor Leishmania major mutants lacking LPG PG sc␤Gal residues can be maintained in the natural L. major host Phleobotomus papatasi (10,11).…”