Digestion of haemoglobin by schistosomes

Mo Klinkert 1and Werner Kunz 2

1 Istituto di Biologia Cellulare, Consiglio Nazionale delle Ricerche, Rome, Italy

2 Institut für Genetik, Heinrich-Heine Universität, Düsseldorf, Germany

A recent article by Dalton et al. (1) sought to provide an update on the digestion of haemoglobin by schistosomes, a mechanism by which the parasite is thought to obtain its amino acids for growth and development. The authors concluded that there are several proteolytic enzymes involved in haemoglobin degradation, contrary to the traditional view that a cysteine proteinase is the major digestive enzyme (2). In so doing, they attempted to clarify the otherwise confusing nomenclature used to describe various enzymes with apparent "haemoglobinolytic activities". The proteinases selected by the authors as possibly having some function in the breakdown of host haemoglobin include two cysteine proteinases, cathepsin B (Sm31) and cathepsin L, an asparaginyl proteinase (Sm32), an aspartyl proteinase (cathepsin D) and dipeptidylpeptidases.

In their discussion on cathepsin L, Dalton et al. have been somewhat overenthusiastic in suggesting cathepsin L as a major digestive enzyme. The fact that specific activity of cathepsin L is "many times greater than that of cathepsin B" does not necessarily lead to the conclusion that cathepsin L plays a "leading role" in haemoglobin degradation. Until experimental evidence is available, such an observation cannot provide sufficient argument for a function in nutrition.

Indeed, there are at least two variant forms of cathepsin L in Schistosoma mansoni. The one referred to by Dalton et al. is encoded by pSmCL1 (March 1994, Genbank accession number U07345) (3), and the other by a cDNA sequence 5C6 (April 1994, Genbank Z32529) (4). While 5C6 shows 54 % identity to mature mouse cathepsin L, pSmCL1 has 45.4 % identity. As the two sequences share only 40 % identity, these are clearly different enzymes. It is possible that they perform totally diverse functions in the schistosome. Resolution of this issue must await studies on localization in the parasite, and a comparison of their biochemical properties, assuming that active recombinant enzymes can be produced or made available.

We argue against 5C6 cathepsin L being a major haemoglobin degrading enzyme, based on its localization in structures associated with the reproductive system of the parasite. Immunohistological experiments have shown 5C6 cathepsin L to be present in vitelloduct, ovovitelloduct, ootype and uterus of the female and in the subtegumental cells of the gynaecorphoric canal of the male. Cathepsin L could be involved in altering the viscosity of fluids in the various ducts to facilitate "easy migration" of vitelline cells or eggs. Recently, J. H. McKerrow and coworkers reported at the Gordon Research Conference on Parasitism (25 - 30 June, 1995) that treatment of S. mansoni-infected mice with an inhibitor of cathepsin L (Morphilino-F-homoF-FMK), led to a significant reduction in egg production by the female. Presumably, McKerrow and colleagues are referring to 5C6 cathepsin L, since their results also suggest an association of the enzyme in the reproductive organs.

Our recent isolation of a S. mansoni cathepsin C cDNA (April 1994, Accession number Z32531) (5) adds to the array of schistosome proteinases, the functions of which are still controversial. It will be a continuing challenge to determine the nature of proteolytic enzymes present in the digestive tract, and to understand the connection between these proteinases and the in vitro and in vivo digestion of haemoglobin.

References

1) Dalton, J.P. et al. (1995) Parasitol. Today 11, 299-303.

2) Dresden, M.H. and Deelder, A.M. (1979) Exp. Parasitol. 48, 190-197.

3) Smith, A.M. et al. (1994) Mol. Biochem. Parasitol. 67, 11-19.

4) Michel, A. et al. (1995) Mol. Biochem. Parasitol., in press

5) Butler, R. et al. (1995) Prot. Pept. Letts., in press.