Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors.

Abstract

The mammalian form of the protozoan parasite Leishmania mexicana contains high activity of a cysteine proteinase (LmCPb) encoded on a tandem array of 19 genes (lmcpb). Homozygous null mutants for lmcpb have been produced by targeted gene disruption. All life-cycle stages of the mutant can be cultured in vitro, demonstrating that the gene is not essential for growth or differentiation of the parasite. However, the mutant exhibits a marked phenotype affecting virulence-- its infectivity to macrophages is reduced by 80%. The mutants are as efficient as wild-type parasites in invading macrophages but they only survive in a small proportion of the cells. However, those parasites that successfully infect these macrophages grow normally. Despite their reduced virulence, the mutants are still able to produce subcutaneous lesions in mice, albeit at a slower rate than wild-type parasites. The product of a single copy of lmcpb re-expressed in the null mutant was enzymatically active and restored infectivity toward macrophages to wild-type levels. Double null mutants created for lmcpb and lmcpa (another cathepsin L-like cysteine proteinase) have a similar phenotype to the lmcpb null mutant, showing that LmCPa does not compensate for the loss of LmCPb.

050100150'98'00'02'04'06'08'10'12'14'16
Citations per Year

922 Citations

Semantic Scholar estimates that this publication has 922 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Mottram1996EvidenceFD, title={Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors.}, author={Jeremy C Mottram and Augustine E. Souza and James E Hutchison and Richard M. Carter and Mhairi J. Frame and Graham H. Coombs}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={1996}, volume={93 12}, pages={6008-13} }