Picture of a sphere with binary code

Making Strathclyde research discoverable to the world...

The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs. It exposes Strathclyde's world leading Open Access research to many of the world's leading resource discovery tools, and from there onto the screens of researchers around the world.

Explore Strathclyde Open Access research content

Influence of parasite encoded inhibitors of serine peptidases in early infection of macrophages with Leishmania major

Eschenlauer, Sylvain C P and Faria, Marilia S and Morrison, Lesley S and Bland, Nicolas and Ribeiro-Gomes, Flavia L and DosReis, George A and Coombs, Graham H and Lima, Ana Paula C A and Mottram, Jeremy C (2008) Influence of parasite encoded inhibitors of serine peptidases in early infection of macrophages with Leishmania major. Cellular Microbiology, 11 (1). pp. 106-120. ISSN 1462-5814

Full text not available in this repository. (Request a copy from the Strathclyde author)

Abstract

Ecotin is a potent inhibitor of family S1A serine peptidases, enzymes lacking in the protozoan parasite Leishmania major. Nevertheless, L. major has three ecotin-like genes, termed inhibitor of serine peptidase (ISP). ISP1 is expressed in vector-borne procyclic and metacyclic promastigotes, whereas ISP2 is also expressed in the mammalian amastigote stage. Recombinant ISP2 inhibited neutrophil elastase, trypsin and chymotrypsin with Kis between 7.7 and 83 nM. L. major ISP2-ISP3 double null mutants (-isp2/3) were created. These grew normally as promastigotes, but were internalized by macrophages more efficiently than wild-type parasites due to the upregulation of phagocytosis by a mechanism dependent on serine peptidase activity. -isp2/3 promastigotes transformed to amastigotes, but failed to divide for 48 h. Intracellular multiplication of -isp2/3 was similar to wild-type parasites when serine peptidase inhibitors were present, suggesting that defective intracellular growth results from the lack of serine peptidase inhibition during promastigote uptake. -isp2/3 mutants were more infective than wild-type parasites to BALB/c mice at the early stages of infection, but became equivalent as the infection progressed. These data support the hypothesis that ISPs of L. major target host serine peptidases and influence the early stages of infection of the mammalian host.