Lipophosphoglycan and secreted acid phosphatase of Leishmania tropica share species-specific epitopes

Jaffe, Charles L.; Perez, M. Leonor; Schnur, Lionel F.

doi:10.1016/0166-6851(90)90186-p

Cited by 44 publications

(11 citation statements)

References 21 publications

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“…Early immunochemical and biochemical analyses indicated that these heavily glycosylated proteins were modified with similar phosphoglycans to those found on the LPG of the same parasites (28,162). Subsequent studies showed that serine residues in the protein backbone of the SAP were modified with Man-1-PO 4 , which was extended with short linear chains of ␣1-2-linked mannose or longer chains of repeating Gal␤1-4Man␣1-PO 4 -phosphodisaccharides (157,185,224).…”

Section: Protein Phosphoglycosylationmentioning

confidence: 99%

Secretory Pathway of Trypanosomatid Parasites

McConville

Mullin

Ilgoutz

et al. 2002

Microbiol Mol Biol Rev

222

191

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The Trypanosomatidae comprise a large group of parasitic protozoa, some of which cause important diseases in humans. These include Trypanosoma brucei (the causative agent of African sleeping sickness and nagana in cattle), Trypanosoma cruzi (the causative agent of Chagas' disease in Central and South America), and Leishmania spp. (the causative agent of visceral and [muco]cutaneous leishmaniasis throughout the tropics and subtropics). The cell surfaces of these parasites are covered in complex protein- or carbohydrate-rich coats that are required for parasite survival and infectivity in their respective insect vectors and mammalian hosts. These molecules are assembled in the secretory pathway. Recent advances in the genetic manipulation of these parasites as well as progress with the parasite genome projects has greatly advanced our understanding of processes that underlie secretory transport in trypanosomatids. This article provides an overview of the organization of the trypanosomatid secretory pathway and connections that exist with endocytic organelles and multiple lytic and storage vacuoles. A number of the molecular components that are required for vesicular transport have been identified, as have some of the sorting signals that direct proteins to the cell surface or organelles in the endosome-vacuole system. Finally, the subcellular organization of the major glycosylation pathways in these parasites is reviewed. Studies on these highly divergent eukaryotes provide important insights into the molecular processes underlying secretory transport that arose very early in eukaryotic evolution. They also reveal unusual or novel aspects of secretory transport and protein glycosylation that may be exploited in developing new antiparasite drugs

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Section: Protein Phosphoglycosylationmentioning

confidence: 99%

Secretory Pathway of Trypanosomatid Parasites

McConville

Mullin

Ilgoutz

et al. 2002

Microbiol Mol Biol Rev

222

191

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“…It is unfortunate that in humans and animal models the T-cell responses to gp63 have been variable. However, when detected, they appeared to be of the Th1 type (59,89,117). Overall, gp63 is still considered a promising vaccine candidate.…”

Section: Expression Of Immunogens In Bacteria and Virusesmentioning

confidence: 99%

Leishmaniasis: Current Status of Vaccine Development

2001

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Leishmaniae are obligatory intracellular protozoa in mononuclear phagocytes. They cause a spectrum of diseases, ranging in severity from spontaneously healing skin lesions to fatal visceral disease. Worldwide, there are 2 million new cases each year and 1/10 of the world's population is at risk of infection. To date, there are no vaccines against leishmaniasis and control measures rely on chemotherapy to alleviate disease and on vector control to reduce transmission. However, a major vaccine development program aimed initially at cutaneous leishmaniasis is under way. Studies in animal models and humans are evaluating the potential of genetically modified live attenuated vaccines, as well as a variety of recombinant antigens or the DNA encoding them. The program also focuses on new adjuvants, including cytokines, and delivery systems to target the T helper type 1 immune responses required for the elimination of this intracellular organism. The availability, in the near future, of the DNA sequences of the human and Leishmania genomes will extend the vaccine program. New vaccine candidates such as parasite virulence factors will be identified. Host susceptibility genes will be mapped to allow the vaccine to be targeted to the population most in need of protection

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“…LPG has a tetrapartite structure consisting of a lysoalkyl-sn-glycerophosphatidyl inositol membrane anchor, a phosphosaccharide core, phosphorylated oligosaccharide repeats and, mannose-and galactosecontaining oligosaccharide caps at the non-reducing end (Turco and Descoteaux, 1992;McConville and Ferguson, 1993;llg et al, 1994b). Moreover, Leishmania covalently modify polypeptides by phosphoglycans, as initially suggested by the reaction of monoclonal antibodies (mAbs) specific for oligosaccharide caps or phosphosaccharide repeats of LPG with secreted proteins (Jaffe et al, 1990;llg et al, 1991a and by specific chemical deglycosylation (Bates et al, 1990). …”

Section: Introductionmentioning

confidence: 99%

Ser/Thr-rich repetitive motifs as targets for phosphoglycan modifications in Leishmania mexicana secreted acid phosphatase.

et al. 1995

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The insect stage of the protozoan parasite Leishmania mexicana secretes a phosphomonoesterase in the form of a filamentous complex. The polypeptide subunits of this polymer are modified by phosphoglycans and/or oligomannosyl residues linked to phosphoserine. Based on peptide sequence data of a predominant 100 kDa protein of the filamentous complex, two tandemly arranged, single copy genes, Imsapl and lmsap2, were cloned and sequenced. Imsapl predicts a protein with features characteristic of acid phosphatases and a remarkable serine-and threonine-rich region of 32 amino acids close to the C-terminus. In the otherwise identical lmsap2 product, this region is extended to 383 amino acids and is composed of short Ser/Thr-rich repeats. Deletion analysis demonstrates that lmsapl encodes the major 100 kDa protein of the complex while a minor 200 kDa component is derived from the lmsap2 gene. Null mutants of either gene retain the ability to secrete acid phosphatase filaments, while a deletion of both genes results in Leishmania defective in enzyme formation. The Ser/Thr-rich domains are the targets for phosphoglycan modifications as shown by the expression of secreted fusion proteins composed of these C-terminal regions and the N-terminal domain of a lysosomal acid phosphatase.

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Lipophosphoglycan and secreted acid phosphatase of Leishmania tropica share species-specific epitopes

Cited by 44 publications

References 21 publications

Secretory Pathway of Trypanosomatid Parasites

Secretory Pathway of Trypanosomatid Parasites

Leishmaniasis: Current Status of Vaccine Development

Ser/Thr-rich repetitive motifs as targets for phosphoglycan modifications in Leishmania mexicana secreted acid phosphatase.

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