We have set up an assay to study the interactions of live pathogens with their hosts by using
protein and
glycosaminoglycan arrays probed by surface plasmon resonance imaging. We have used this assay to characterize the interactions of Leishmania promastigotes with ~70 mammalian host biomolecules (extracellular
proteins,
glycosaminoglycans,
growth factors,
cell surface receptors). We have identified, in total, 27 new partners (23
proteins, 4
glycosaminoglycans) of procyclic promastigotes of six Leishmania species and 18 partners (15
proteins, 3
glycosaminoglycans) of three species of stationary-phase promastigotes for all the strains tested. The diversity of the interaction repertoires of Leishmania parasites reflects their dynamic and complex interplay with their mammalian hosts, which depends mostly on the species and strains of Leishmania. Stationary-phase Leishmania parasites target
extracellular matrix proteins and
glycosaminoglycans, which are highly connected in the extracellular interaction network.
Heparin and
heparan sulfate bind to most Leishmania strains tested, and 6-O-sulfate groups play a crucial role in these interactions. Numerous Leishmania strains bind to
tropoelastin, and some strains are even able to degrade it. Several strains interact with
collagen VI, which is expressed by macrophages. Most Leishmania promastigotes interact with several regulators of angiogenesis, including antiangiogenic factors (
endostatin,
anastellin) and proangiogenic factors (ECM-1,
VEGF, and TEM8 [also known as
anthrax toxin receptor 1]), which are regulated by
hypoxia. Since
hypoxia modulates the
infection of macrophages by the parasites, these interactions might influence the
infection of host cells by Leishmania.