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Theresa H T Coetzer

Theresa H T Coetzer
University of KwaZulu-Natal Pietermaritzburg South Africa · School of Life Sciences

PhD

About

61
Publications
5,148
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Introduction
Research focus: proteolytic enzymes as diagnostic & drug targets in African parasitic diseases: trypanosomiasis, trichinellosis and theileriosis. Expertise in producing chicken antibodies against whole proteins & peptides corresponding to epitopes identified in silico. Chicken egg yolk antibodies (IgY) are powerful immunochemical tools that find wide application in research. Holds a DSI-NRF South African Research Chair Initiative (SARChI) Chair in Proteolysis in Haemostasis, Health and Disease.
Additional affiliations
January 2016 - present
University of KwaZulu-Natal, Pietermaritzburg, South Africa
Position
  • Chair
Description
  • Research and supervision of postgraduate students
March 2006 - present
University of KwaZulu-Natal
Position
  • Professor (Full)
Description
  • Structure-function of amino acids and proteins; immunology; immunochemical techniques
January 2001 - February 2006
University of Natal
Position
  • Professor (Associate)
Description
  • Introductory Biochemistry, Immunology, Immunochemical techniques
Education
January 1989 - April 1993
University of Natal
Field of study
  • Biochemistry
January 1983 - February 1984
Stellenbosch University
Field of study
  • Biochemistry
February 1982 - December 1982
Stellenbosch University
Field of study
  • Biochemistry

Publications

Publications (61)
Article
Full-text available
The protozoan parasite Trypanosoma evansi is responsible for causing surra in a variety of mammalian hosts and is spread by many vectors over a wide geographical area making it an ideal target for irradiation as a tool to study the initial events that occur during infection. Parasites irradiated at the representative doses 100Gy, 140Gy, and 200Gy w...
Article
Trypanosomes, which cause animal African trypanosomiasis, escape host immune responses by renewing their variable surface glycoprotein (VSG) coat. Chemotherapy is currently the only form of external intervention available. However, the efficacy of current trypanocides is poor due to overuse leading to an increase in drug resistance. Major surface p...
Article
Crocodile immunity has not been fully characterised with more studies on crocodile innate immunity than cell-mediated or humoral immunity. Crocodile immunoglobulin genes have been described but immunoglobulin proteins have not been isolated or studied biochemically. Two large proteins proposed to be crocodile IgM and IgY were isolated and purified...
Article
Copper is an essential component of cuproproteins but can be toxic to cells, therefore copper metabolism is very carefully regulated within cells. To gain insight into trypanosome copper metabolism, Trypanosoma spp. genomic databases were screened for the presence of copper-containing and -transporting proteins. Among other genes encoding copper-bi...
Article
The metacaspases (MCAs) are attractive drug targets for the treatment of African trypanosomiasis as they are not found in the metazoan kingdom and their action has been implicated in cell cycle and cell death pathways in kinetoplastid parasites. Here we report the biochemical characterisation of MCA5 from T. congolense. Upon recombinant expression...
Article
African animal trypanosomosis (nagana) is caused by tsetse-transmitted protozoan parasites. Their cysteine proteases are potential chemotherapeutic and diagnostic targets. The N-glycosylated catalytic domain of Trypanosoma vivax cathepsin L-like cysteine protease, rTviCATLcat, was recombinantly expressed and purified from culture supernatants while...
Article
Full-text available
The protozoan parasite Trypanosoma evansi is responsible for causing Surra in a variety of mammalian hosts over a wide geographical area. In the absence of an effective vaccine and increasing resistance to current chemotherapeutic agents, peptidases from the S9 prolyl oligopeptidase family have been identified as potential drug and vaccine targets....
Article
Malaria rapid diagnostic tests (RDTs) are immunochromatographic tests detecting Plasmodial Histidine rich protein 2 (HRP2), lactate dehydrogenase (LDH) and aldolase. HRP2 is only expressed by Plasmodium falciparum parasites and the protein is not expressed in several geographic isolates. LDH-based tests lack sensitivity compared to HRP2 tests. This...
Article
Parasitic infections are among the leading global public health problems with very high economic and mortality burdens. Unfortunately, the available treatment drugs are beset with side effects and continuous parasite drug resistance is being reported. However, new findings reveal more promising compounds especially of plant origin. Among the promis...
Article
Full-text available
The human retinoblastoma binding protein 6 (RBBP6) is implicated in esophageal, lung, hepatocellular and colon cancers. Furthermore, RBBP6 was identified as a strong marker for colon cancer prognosis and as a predisposing factor in familial myeloproliferative neoplasms. Functionally, the mammalian protein interacts with p53 and enhances the activit...
Article
Trypanosoma congolense is a haemoprotozoan parasite that causes African animal trypanosomosis a wasting disease of cattle and small ruminants. Current control methods are unsatisfactory and no conventional vaccine exists due to antigenic variation. An anti-disease vaccine approach to control T.congolense has been proposed requiring the identificati...
Article
Full-text available
Background: Mutants of the serine protease, mannose-binding lectin associated-protease-3 (MASP-3), are associated with Carnevale, Mingarelli, Malpuech and Michels (3MC) syndrome. Results: The lack of activity and the structure of the G666E mutant of MASP-3 reveals a molecular basis for 3MC syndrome. Conclusion: Mutants of MASP-3 associated with 3MC...
Article
Full-text available
The mannose-binding lectin associated-protease-3 (MASP-3) is a member of the lectin pathway of the complement system, a key component of human innate and active immunity. Mutations in MASP-3 have recently been found to be associated with Carnevale, Mingarelli, Malpuech, and Michels (3MC) syndrome, a severe developmental disorder manifested by cleft...
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Article
Full-text available
The serine protease, C1r, initiates activation of the classical pathway of complement, which is a crucial innate defense mechanism against pathogens and altered-self cells. C1r both autoactivates and subsequently cleaves and activates C1s. Because complement is implicated in many inflammatory diseases, an understanding of the interaction between C1...
Article
Full-text available
The classical pathway of complement is crucial to the immune system, but it also contributes to inflammatory diseases when dysregulated. Binding of the C1 complex to ligands activates the pathway by inducing autoactivation of associated C1r, after which C1r activates C1s. C1s cleaves complement component C4 and then C2 to cause full activation of t...
Article
Full-text available
Background We investigated several adjuvants for their effects on the humoral immune response in both mice and cattle using the central domain of congopain (C2), the major cysteine protease of Trypanosoma congolense, as a model for developing a vaccine against animal trypanosomosis. The magnitude and sustainability of the immune response against C2...
Article
African trypanosomosis is a parasitic disease in man and animals caused by protozoan parasites of the genus Trypanosoma. Nagana, the cattle form of the disease, is caused by Trypanosoma congolense, Trypanosoma vivax and Trypanosoma brucei brucei. An option for developing vaccines and chemotherapeutic agents against trypanosomosis is to target patho...
Article
The complement system is fundamental to both innate and adaptive immunity and can be initiated via the classical, lectin or alternative pathways. Cleavage of C4 by MASP-2, the initiating protease of the lectin pathway, is a crucial event in the activation of this pathway, preceding the eventual formation of the C3 convertase (C4bC2a) complex on the...
Article
Trypanosoma brucei brucei are tsetse-transmitted, extracellular protozoan parasite that causes Nagana, a cattle disease similar to sleeping sickness caused in humans by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. Proteases of these parasites have come under increasing scrutiny because of their importance in such aspects as dise...
Article
African animal trypanosomosis (nagana) is arguably the most important parasitic disease affecting livestock in sub-Saharan Africa. Since none of the existing control measures are entirely satisfactory, vaccine development is being actively pursued. However, due to antigenic variation, the quest for a conventional vaccine has proven elusive. As a re...
Article
Congopain, the major cysteine peptidase of Trypanosoma congolense is an attractive candidate for an anti-disease vaccine and target for the design of specific inhibitors. A complicating factor for the inclusion of congopain in a vaccine is that multiple variants of congopain are present in the genome of the parasite. In order to determine whether t...
Article
Malaria lactate dehydrogenase, a glycolytic enzyme, is a malaria diagnostic target in lateral flow immunochromatographic rapid diagnostic tests. Recombinant Plasmodium yoelii LDH was cloned into the pET-28a vector, expressed and the expressed protein purified from a Ni-NTA affinity matrix. A pan-malarial LDH antibody directed against a common malar...
Article
The newly excysted juvenile (NEJ) stage of the Fasciola hepatica lifecycle occurs just prior to invasion into the wall of the gut of the host, rendering it an important target for drug development. The cathepsin B enzymes from NEJ flukes have recently been demonstrated to be crucial to invasion and migration by the parasite. Here we characterize on...
Article
Full-text available
The protozoan parasite Trypanosoma congolense is the main causative agent of livestock trypanosomosis. Congopain, the major lysosomal cysteine proteinase of T. congolense, contributes to disease pathogenesis, and antibody-mediated inhibition of this enzyme may contribute to mechanisms of trypanotolerance. The potential of different adjuvants to fac...
Article
Full-text available
Cysteine proteases have been shown to be essential virulence factors and drug targets in trypanosomatids and an attractive antidisease vaccine candidate for Trypanosoma congolense. Here, we describe an important amplification of genes encoding cathepsin B-like proteases unique to T. congolense. More than 13 different genes were identified, whereas...
Article
Oligopeptidase B is a "processing peptidase" from the prolyl oligopeptidase family of serine peptidases present in Gram negative bacteria, protozoa and plants. Unlike the prototype prolyl oligopeptidase, oligopeptidase B hydrolyses peptides on the carboxyl side of pairs of basic amino acid residues. Molecular modelling and mutation studies have ide...
Chapter
Animals interact daily with each of us as they sing a dawn chorus, provide us with companionship, food and sustenance (draft animals) and wild animals fascinate us in their natural environment. South Africa has eleven official languages, reflecting the country's ethnic and multi-cultural diversity. The way in which animals are treated is often clos...
Article
Antibodies against primaquine, pyrimethamine, dapsone, tetracycline, and doxycycline were raised in chickens inoculated with each drug conjugated to a rabbit albumin carrier. Antibody titres against drug and carrier were highest during week 6 postinoculation. Affinity purified anti-primaquine antibodies did not recognise other drugs, but affinity p...
Article
Separating individual proteins from complex mixtures of molecules is the basis of many biochemical investigations. The method describes the separation of immunoglobulin Y (IgY) from chicken eggs using a series of physical and chemical separation techniques. The separation is rapid, and the success of each step is readily viewed on an SDS-polyacryla...
Article
The closely related serpins squamous cell carcinoma antigen-1 and -2 (SCCA-1 and -2, respectively) are capable of inhibiting cysteine proteases of the papain superfamily. To ascertain whether the ability to inhibit cysteine proteases is an intrinsic property of serpins in general, the reactive center loop (RCL) of the archetypal serine protease inh...
Article
Full-text available
MENT (Myeloid andErythroid Nuclear Termination stage-specific protein) is a developmentally regulated chromosomal serpin that condenses chromatin in terminally differentiated avian blood cells. We show that MENT is an effective inhibitor of the papain-like cysteine proteinases cathepsins L and V. In addition, ectopic expression of MENT in mammalian...
Article
Full-text available
A trypsin-like serine peptidase activity, levels of which correlate with blood parasitemia levels, is present in the plasma of rats acutely infected with Trypanosoma brucei brucei. Antibodies to a trypanosome peptidase with a trypsin-like substrate specificity (oligopeptidase B [OP-Tb]) cross-reacted with a protein in the plasma of trypanosome-infe...
Article
Two groups of irreversible serine peptidase inhibitors, peptidyl chloromethyl ketones and peptidyl phosphonate diphenyl esters, were examined for antitrypanosomal activity against the bloodstream form of Trypanosoma brucei brucei. Both peptidyl chloromethyl ketones and peptidyl phosphonate diphenyl esters inhibited trypsin-like peptidases of the pa...
Article
Full-text available
Protozoan parasites of the genus Trypanosoma cause disease in a wide range of mammalian hosts. Trypanosoma brucei brucei, transmitted by tsetse fly to cattle, causes a disease (Nagana) of great economic importance in parts of Africa. T. b. brucei also serves as a model for related Trypanosoma species, which cause human sleeping sickness. Chalcone a...
Article
Full-text available
Trypanosoma brucei contains a soluble serine oligopeptidase (OP-Tb) that is released into the host bloodstream during infection, where it has been postulated to participate in the pathogenesis of African trypanosomiasis. Here, we report the identification of a single copy gene encoding the T. brucei oligopeptidase and a homologue from the related t...
Article
Trypanosoma brucei contain a serine oligopeptidase (OP-Tb) that is released into (and remains active in) the blood of trypanosome-infected animals. Here a similar enzyme from Trypanosoma congolense is described. This oligopeptidase, called OP-Tc, was purified using three-phase partitioning, and ion-exchange and affinity chromatography. OP-Tc is inh...
Article
Trypanosoma brucei brucei is a causative agent of bovine trypanosomiasis (nagana), a disease of considerable economic significance in much of Africa. Here we report investigations on the effects of various irreversible cysteine proteinase inhibitors, including vinyl sulfones (VS), peptidyl chloromethylketones (CMK), diazomethylketones, and fluorome...
Article
African trypanosomes contain a cytosolic serine oligopeptidase, called OP-Tb, that is reversibly inhibited by the active principles of three of the five most commonly used trypanocidal drugs: pentamidine, diminazene and suramin. OP-Tb was inhibited by pentamidine in a competitive manner, and by suramin in a partial, non-competitive manner. The inhi...
Article
Anti-peptide antibodies were produced against the cysteine proteinase trypanopain-Tb from Trypanosoma brucei brucei and the effects of these antibodies on enzyme activity against carboxybenzoyl (Z)-Phe-Arg-aminomethylcoumarin (AMC) investigated. A peptide was synthesised corresponding to a region of the trypanopain-Tb active site around the active...
Article
African trypanosomes are tsetse-transmitted protozoan parasites that cause sleeping sickness in humans and 'Nagana' in animals. A high relative molecular mass multicatalytic proteinase complex (MCP) was purified and biochemically characterized from the cytosolic fraction of Trypanosoma brucei brucei. The isolation procedure consisted of fractionati...
Article
In vitro, living bloodstream forms of Trypanosoma congolense were shown to hydrolyse p-nitrophenyl phosphate, a substrate for phosphatases. This activity appears to be from an acid phosphatase because it was enhanced at low pH values, was inhibited by the acid phosphatase inhibitor sodium fluoride, and was not inhibited by the alkaline phosphatase...
Article
African trypanosomes contain proteases that may be released into the bloodstream of their infected hosts. This paper describes a novel, combined isolation of a cysteine proteinase (called trypanopain-Tb) and a serine oligopeptidase (which we call oligopeptidase-Tb) from Trypanosoma brucei brucei, as well as a comparison of the activities of these t...
Article
Cathepsin L and stefin B were isolated from sheep liver, the cathepsin L being isolated by a low pH homogenisation method, which increases the proportion of the two-chain form of the enzyme, thus facilitating sequencing. The amino acid sequences of the isolated cathepsin L and stefin B were determined. The two-chain form of cathepsin L contains 217...
Article
Full-text available
Adhesins from oral bacteria perform an important function in colonizing target tissues within the dentogingival cavity. In Porphyromonas gingivalis certain of these adhesion proteins exist as a complex with either of two major proteinases referred to as gingipain R (arginine-specific gingipain) and gingipain K (lysine-specific gingipain) (R. N. Pik...
Article
The activity of cathepsin L is affected by ionic strength, resulting in the measured pH optimum being higher in acetate-4-morpholineethane sulfonic acid (MES)-Tris buffers of constant ionic strength than in phosphate buffers of constant molarity (and hence varying ionic strength). In acetate-MES-Tris and phosphate buffers of constant ionic strength...
Article
Cathepsin L was purified from the liver of a higher primate, the baboon (Papio ursinus), largely in a single-chain form and in the form of proteolytically active complexes with an endogenous cystatin. This mimics the situation found in both human and sheep livers. Both forms of cathepsin L were active at physiological pH. Physicochemical characteri...
Article
An unusual bacterium causing respiratory disease in chickens emerged in South Africa in February 1989. The disease resembled infectious coryza but the organism differed from typical Haemophilus paragallinarum especially in that it did not require V-factor for growth. It has been termed an NAD-independent H. paragallinarum. A study of avian haemophi...
Article
Antibodies, raised in chickens (IgY) and rabbits (IgG) against the lysosomal proteinase cathepsin L, targeted the enzyme in an ELISA and Western blot. In contrast to the rabbit IgG, the chicken IgY was immunoinhibitory towards cathepsin L. An epitope that elicits immunoinhibitory antibodies has been localized to an active site-associated peptide se...
Article
The activity of single-chain cathepsin L was found to be markedly dependent on cysteine concentration, while a covalent, proteolytically active cathepsin L/cystatin complex was less cysteine-dependent. Cysteine levels and ionic strength did not affect the stability of either enzyme form and both enzyme forms were found to be stable for significant...
Article
Proteolytically active complexes of the proteinase cathepsin L, with an endogenous inhibitor of cysteine proteinases, were purified from sheep liver. The complexes were active against the synthetic substrate Z-Phe-Arg-NHMec and also the proteins azocasein and gelatin. The composition of the complexes was demonstrated by Western blotting, after redu...
Article
Anti-peptide antibodies were raised against synthetic peptides selected from the sequences of human cathepsins B and L, porcine cathepsin D and human type IV collagenase. Sequences were selected from the active site clefts of the cathepsins in the expectation that these would elicit immunoinhibitory antibodies. In the case of type IV collagenase a...
Article
Tubers of Callilepis laureola, a traditional remedy, contain an inhibitor of oxidative phosphorylation; atractyloside. A "competitive" ELISA was developed, using the antiserum produced to an atractyloside-protein conjugate. An ovalbumin-atractyloside conjugate was adsorbed to microtitre wells and plates incubated with sample (atractyloside or tuber...
Article
Evidence in support of previous observations by different authors that agarose is not an entirely inert support in affinity chromatography is presented. In the present communication it is shown that 8% granulated agarose adsorb serum glycoproteins in 10mM phosphate buffer, pH 7.2 and desorb these in 200mM NaCl in 10mM phosphate buffer, pH 7.2. The...

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Projects (2)
Project
By understanding the role which metacaspases play in the trypanosomal parasites, it is possible that these peptidases may be diagnostic antigens or targets for the development of novel chemotherapeutics.