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M Dorris

Publications and source records attributed to M Dorris.

7 recordsLinked to original sources
PubMed2001

Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I.

Fab I, enoyl acyl carrier protein reductase (ENR), is an enzyme used in fatty acid synthesis. It is a single chain polypeptide in plants, bacteria, and mycobacteria, but is part of a complex polypeptide in animals and fungi. Certain other enzymes in fatty acid synthesis in apicomplexan parasites appear to have multiple forms, homologous to either a plastid, plant-like single chain enzyme or more like the animal complex polypeptide chain. We identified a plant-like Fab I in Plasmodium falciparum and modelled the structure on the Brassica napus and Escherichia coli structures, alone and complexed to triclosan (5-chloro-2-[2,4 dichlorophenoxy] phenol]), which confirmed all the requisite features of an ENR and its interactions with triclosan. Like the remarkable effect of triclosan on a wide variety of bacteria, this compound markedly inhibits growth and survival of the apicomplexan parasites P. falciparum and Toxoplasma gondii at low (i.e. IC50 congruent with150-2000 and 62 ng/ml, respectively) concentrations. Discovery and characterisation of an apicomplexan Fab I and discovery of triclosan as lead compound provide means to rationally design novel inhibitory compounds.

Amino Acid Sequence↗
PubMed2000

The small subunit ribosomal RNA sequence of Strongyloides stercoralis.

The published small subunit rRNA (ssrRNA) gene sequences for Strongyloides ratti and Strongyloides stercoralis are remarkably divergent, particularly in the 5' 400 bases of the approximately 1700 base pair (bp) sequences. This level of divergence between species nominally in the same genus was unprecedented. We have redetermined the ssrRNA sequence of S. stercoralis and find that the published sequence is a chimaera of parasite and fungal segments. The true sequence for S. stercoralis ssrRNA is very similar to that of S. ratti.

Animals↗
PubMed1999

Analysis of Plasmodium falciparum PfEMP-1/var genes suggests that recombination rearranges constrained sequences.

The var genes of Plasmodium falciparum encode a family of parasite erythrocyte surface antigens, the PfEMP-1 proteins, which function as adhesion ligands for host endothelial and erythrocyte receptors. PfEMP-1 is extremely polymorphic although the extent of this variation in naturally transmitted parasite populations is unclear. We have identified 56 different sequences from the Duffy binding-like (DBL-1) domain of var genes amplified from six different P. falciparum clones isolated from patient infections in a Sudanese village in October-November 1989. These clones have been compared with 25 PfEMP-1 sequences expressed from different var gene loci by the 3D7A clone and 48 PfEMP-1 sequences from different isolates in endemic areas such as Kenya, Brazil, Gambia, Vietnam and Vanuatu to analyse diversity in clonal, local and 'global' P. falciparum populations. Evidence that certain conserved sequences recur in clones from one Sudanese village and in isolates from all over the world suggests that var gene diversity is the result of recombinational reshuffling of a subset of conserved, presumably ancestral sequences. Recurrence of particular var sequence blocks thus leads to 'overlaps' in the PfEMP-1 sequence repertoire of different P. falciparum clones.

Amino Acid Sequence↗
PubMed1999

Molecular analysis of nematode diversity and the evolution of parasitism.

A thorough and coherent classification of the phylum Nematoda is essential if the evolution of countless phenotypes is to be understood. Here, Mark Dorris, Paul De Ley and Mark Blaxter discuss how the application of molecular phylogenetics is helping to resolve some of the inconsistencies in morphological classification and phylogeny by establishing relationships between free-living and parasitic groups, showing possible patterns underlying the origins of parasitism and placing key nematode species in an evolutionary context for comparative study.

Animals↗
PubMed1998

A molecular evolutionary framework for the phylum Nematoda.

Nematodes are important: parasitic nematodes threaten the health of plants, animals and humans on a global scale; interstitial nematodes pervade sediment and soil ecosystems in overwhelming numbers; and Caenorhabditis elegans is a favourite experimental model system. A lack of clearly homologous characters and the absence of an informative fossil record have prevented us from deriving a consistent evolutionary framework for the phylum. Here we present a phylogenetic analysis, using 53 small subunit ribosomal DNA sequences from a wide range of nematodes. With this analysis, we can compare animal-parasitic, plant-parasitic and free-living taxa using a common measurement. Our results indicate that convergent morphological evolution may be extensive and that present higher-level classification of the Nematoda will need revision. We identify five major clades within the phylum, all of which include parasitic species. We suggest that animal parasitism arose independently at least four times, and plant parasitism three times. We clarify the relationship of C. elegans to major parasitic groups; this will allow more effective exploitation of our genetic and biological knowledge of this model species.

Animals↗
PubMed1994

Evidence for a radical mechanism in peroxidase-catalyzed coupling. I. Steady-state experiments with various peroxidases.

Biosynthesis of thyroxine in the thyroid gland involves a reaction between two diiodotyrosyl residues within the same molecule of thyroglobulin, a large, thyroid-specific glycoprotein. This reaction, generally referred to as the coupling reaction, is catalyzed in the thyroid by the heme-containing glycoprotein enzyme, thyroid peroxidase, also a thyroid-specific protein. The coupling reaction is, however, not specific for thyroid peroxidase; it is also efficiently catalyzed by other heme-containing peroxidases. Peroxidase-catalyzed coupling may also occur between a monoiodotyrosyl and a diiodotyrosyl residue in thyroglobulin to form the more potent thyroid hormone, 3',3,5-triiodothyronine. Under most conditions, thyroxine formation in the thyroid is greatly favored over that of 3',3,5-triiodothyronine. Two mechanisms have been proposed for the coupling reaction, a radical mechanism and an ionic mechanism. In this, and in the following paper, we present evidence favoring a radical mechanism. This view is bsed primarily on the observation that peroxidase-catalyzed coupling is markedly stimulated by substoichiometric concentrations of free diiodotyrosine (DIT). Evidence obtained in this and in the following paper leads us to conclude that the stimulatory effect of DIT on coupling involves peroxidase-catalyzed oxidation of the added DIT to a radical form. We propose that this stimulation involves a radical chain propagation mechanism. This implies that peroxidase-catalyzed coupling in the absence of DIT must also be a radical-mediated reaction.

Animals↗