Aspartic protease activities of schistosomes cleave mammalian hemoglobins in a host-specific manner

Koehler, Jeffrey W.; Morales, Maria E.; Shelby, Bryan D.; Brindley, Paul J.

doi:10.1590/s0074-02762007000100014

Cited by 20 publications

(13 citation statements)

References 16 publications

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“…These enzymes play a key role in the digestion of haemoglobin by schistosomes (Brinkworth et al 2001, Koehler et al 2007, Plasmodium falciparum (Francis et al 1997, Banerjee et al 2002, Necator americanus (Brown et al 1995(Brown et al , 1999 and A. caninum (Williamson et al 2003). Interestingly, cysteine protease activity was not detected under the experimental conditions tested.…”

Section: Discussionmentioning

confidence: 94%

Proteolytic activity in the adult and larval stages of the human roundworm parasite Angiostrongylus costaricensis

Rebello¹,

Siqueira

Ribeiro

et al. 2012

Mem. Inst. Oswaldo Cruz

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Section: Discussionmentioning

confidence: 94%

Proteolytic activity in the adult and larval stages of the human roundworm parasite Angiostrongylus costaricensis

Rebello¹,

Siqueira

Ribeiro

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…In support of this, protease activities from S. japonicum (a schistosome with a very wide host range) cleave hemoglobin from bovine, sheep, and horse blood more efficiently than does the activity from extracts of S. mansoni (a schistosome with a limited host range, essentially confined to humans and some rodents) [48].…”

Section: Feeding Via the Alimentary Tractmentioning

confidence: 95%

Schistosome Feeding and Regurgitation

et al. 2014

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Schistosomes are parasitic flatworms that infect >200 million people worldwide, causing the chronic, debilitating disease schistosomiasis. Unusual among parasitic helminths, the long-lived adult worms, continuously bathed in blood, take up nutrients directly across the body surface and also by ingestion of blood into the gut. Recent proteomic analyses of the body surface revealed the presence of hydrolytic enzymes, solute, and ion transporters, thus emphasising its metabolic credentials. Furthermore, definition of the molecular mechanisms for the uptake of selected metabolites (glucose, certain amino acids, and water) establishes it as a vital site of nutrient acquisition. Nevertheless, the amount of blood ingested into the gut per day is considerable: for males ∼100 nl; for the more actively feeding females ∼900 nl, >4 times body volume. Ingested erythrocytes are lysed as they pass through the specialized esophagus, while leucocytes become tethered and disabled there. Proteomics and transcriptomics have revealed, in addition to gut proteases, an amino acid transporter in gut tissue and other hydrolases, ion, and lipid transporters in the lumen, implicating the gut as the site for acquisition of essential lipids and inorganic ions. The surface is the principal entry route for glucose, whereas the gut dominates amino acid acquisition, especially in females. Heme, a potentially toxic hemoglobin degradation product, accumulates in the gut and, since schistosomes lack an anus, must be expelled by the poorly understood process of regurgitation. Here we place the new observations on the proteome of body surface and gut, and the entry of different nutrient classes into schistosomes, into the context of older studies on worm composition and metabolism. We suggest that the balance between surface and gut in nutrition is determined by the constraints of solute diffusion imposed by differences in male and female worm morphology. Our conclusions have major implications for worm survival under immunological or pharmacological pressure.

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“…A cathepsin D aspartic protease, able to degrade human and other mammalian hemoglobins, has been previously described in adults worm extracts from S. mansoni [9,10]. Due to its physiological significance for schistosomes, deeper studies on its molecular and biochemical properties, gene structure and phylogeny have been undertaken [6,11,12].…”

Section: Introductionmentioning

confidence: 99%

RNA interference of Schistosoma mansoni cathepsin D, the apical enzyme of the hemoglobin proteolysis cascade

Morales

Rinaldi

Gobert

et al. 2008

Molecular and Biochemical Parasitology

118

111

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The aspartic protease cathepsin D (Clan AA, Family A1) is expressed in the schistosome gut where it plays an apical role in the digestion of hemoglobin released from ingested erythrocytes. In this report, RNA interference approaches were employed to investigate the effects of knockdown of schistosome cathepsin D. Cultured schistosomules of Schistosoma mansoni were exposed by square wave electroporation to double stranded RNA (dsRNA) specific for cDNA encoding S. mansoni cathepsin D. RNAi mediated reductions in transcript levels led to phenotypic changes including significant growth retardation in vitro and suppression of aspartic protease enzyme activity. In addition, black-pigmented heme, the end point by-product of normal hemoglobin proteolysis that accumulates in the schistosome gut, was not apparent within the guts of the treated schistosomules. Rather, their guts appeared to be red in color, rather than black, apparently indicating the presence of intact rather than digested host hemoglobin. These phenotypic effects were apparent when either of two forms of dsRNA, a long form spanning the entire target transcript or a short form specific for the 3'-region were employed. Off-target effects were not apparent in transcript levels of the gut-localized cysteine protease cathepsin B1. Finally, cathepsin D may be an essential enzyme in the mammal-parasitic stages of schistosomes because schistosomules treated ex vivo with dsRNA did not survive to maturity after transfer into Balb/c mice. These and earlier findings suggest that, given its essential function in parasite nutrition, schistosome cathepsin D could be developed as a target for novel anti-schistosomal interventions.

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Aspartic protease activities of schistosomes cleave mammalian hemoglobins in a host-specific manner

Cited by 20 publications

References 16 publications

Proteolytic activity in the adult and larval stages of the human roundworm parasite Angiostrongylus costaricensis

Proteolytic activity in the adult and larval stages of the human roundworm parasite Angiostrongylus costaricensis

Schistosome Feeding and Regurgitation

RNA interference of Schistosoma mansoni cathepsin D, the apical enzyme of the hemoglobin proteolysis cascade

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