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3. Heme and blood-feeding parasites: friends or foes?

Author

Glanfield Amber, Toh Shu, Gobert Geoffrey N, and Jones Malcolm K

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Hemoparasites, like malaria and schistosomes, are constantly faced with the challenges of storing and detoxifying large quantities of heme, released from their catabolism of host erythrocytes. Heme is an essential prosthetic group that forms the reactive core of numerous hemoproteins with diverse biological functions. However, due to its reactive nature, it is also a potentially toxic molecule. Thus, the acquisition and detoxification of heme is likely to be paramount for the survival and establishment of parasitism. Understanding the underlying mechanism involved in this interaction could possibly provide potential novel targets for drug and vaccine development, and disease treatment. However, there remains a wide gap in our understanding of these mechanisms. This review summarizes the biological importance of heme for hemoparasite, and the adaptations utilized in its sequestration and detoxification.

Published
2010
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5. Two isoforms of a divalent metal transporter (DMT1) in schistosoma mansoni suggest a surface-associated pathway for iron absorption in schistosomes

Author

Smyth, Danielle, Glanfield, Amber, McManus, Donald, Hacker, Elke, Blair, David, Anderson, Greg, Jones, Malcolm, Smyth, Danielle, Glanfield, Amber, McManus, Donald, Hacker, Elke, Blair, David, Anderson, Greg, and Jones, Malcolm

Abstract

We describe two homologues of the mammalian divalent metal transporter (DMT1) for Schistosoma mansoni, a pathogenic intravascular parasite of humans. Schistosomes have a high nutritional and metabolic demand for iron. Nucleotide sequences of the parasite homologues, designated SmDMT1A and -B, are identical in all but the 5′-regions. The predicted amino acid sequences share at least 60% identity with DMT1 (=Nramp2) of humans, mice, and rats, and at least 55% identity with Nramp1 from mice, humans and Caenorhabditis elegans. SmDMT1A is expressed in differentiating eggs, miracidia, cercariae, schistosomula, and adults, whereas SmDMT1B is expressed in all but the miracidium and occurs at lower levels than SmDMT1A in differentiating eggs and cercariae. An iron-responsive element, present at the 3′-untranslated region of many DMT1 molecules, is not present in schistosome mRNAs studied here. A Western blot analysis of adult worm preparations using a homologous rabbit serum raised against a schistosome DMT1 peptide and a heterologous serum raised against mammalian DMT1, revealed a band approximating 115 kDa. By immunofluorescence microscopy, the schistosome DMT1s localize primarily to the tegument. Iron uptake assays demonstrated that SmDMT1s were able to rescue yeast growth in ferrous iron-transport deficient yeast (fet3fet4). The results suggest that schistosomes express molecules for ferrous iron transport in their tegument, suggesting trans-tegumental transport as one means of iron acquisition for these parasites.

Published
2006

16. Heme and blood-feeding parasites: friends or foes?

Author

Shu Qin Toh, Glanfield, Amber, Gobert, Geoffrey N., and Jones, Malcolm K.

Subjects
*PARASITES, *PORPHYRINS, *HEMOGLOBINS, *DETOXIFICATION (Alternative medicine), *PREVENTIVE medicine, *METALLOPROTEINS, *PREDATION, *PROTOZOAN diseases, *VACCINATION, *MALARIA
Abstract

Hemoparasites, like malaria and schistosomes, are constantly faced with the challenges of storing and detoxifying large quantities of heme, released from their catabolism of host erythrocytes. Heme is an essential prosthetic group that forms the reactive core of numerous hemoproteins with diverse biological functions. However, due to its reactive nature, it is also a potentially toxic molecule. Thus, the acquisition and detoxification of heme is likely to be paramount for the survival and establishment of parasitism. Understanding the underlying mechanism involved in this interaction could possibly provide potential novel targets for drug and vaccine development, and disease treatment. However, there remains a wide gap in our understanding of these mechanisms. This review summarizes the biological importance of heme for hemoparasite, and the adaptations utilized in its sequestration and detoxification. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

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