Roderick AM Williams

University of the West of Scotland | UWS · School of Science

Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC50 values < 20 µg/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry...

Acanthamoeba keratitis (AK) is a sight threatening infection caused by the free-living amoeba Acanthamoeba. This infection is largely associated with contact lens wear and the recent increase in AK incidences highlights the ineffectiveness of existing curative and preventative treatments. Current curative and protective treatments being active in p...

Miltefosine (Milt) is the only oral treatment for visceral leishmaniasis (VL) but its use is associated with adverse effects, e.g., teratogenicity, vomiting, diarrhoea. Understanding how its chemical structure induces cytotoxicity, whilst not compromising its anti-parasitic efficacy, could identify more effective compounds. Therefore, we systemical...

Leishmania is a parasite that causes the disease leishmaniasis, and 700 000 to 1 million new cases occur each year. There are few drugs that treat the disease and drug resistance in the parasite limits the clinical utility of existing drugs. One way to combat drug resistance is to use combination therapy rather than monotherapy. In this study we ha...

The opportunistic pathogen, Acanthamoeba castellanii is the causative agent for the sight threatening infection Acanthamoeba keratitis (AK). It is commonly associated with contact lens wearers, and prevalence is increasing at an alarming rate due to an inadequate preventive strategy to protect the lens from this protist. This problem is compounded...

The direct impacts of anthropogenic pollution are widely known public and environmental health concerns, and details on the indirect impact of these are starting to emerge, for example affecting the environmental microbiome. Anthropogenic activities throughout history with associated pollution burdens are notable contributors. Focusing on the histo...

There are five species of Plasmodium that infect humans, of which the most serious is Plasmodium falciparum. Genetic studies have been useful in determining the biosynthetic pathways that take place within the parasite, and in identifying potential drug targets for potential novel antimalarial drugs. The life cycle of the parasite is complex, invol...

We report for the first time the isolation of 2-furyl(phenyl)methanol (5) from the chloroform extracts of the Atractylis gummifera roots. A. gummifera is a thistle belonging to the Asteraceae family that produces the ent-kaurane diterpenoid glycoside atractyloside (ATR). ATR (1) was isolated and chemically modified to obtain its aglycone atractylig...

Extracts of 35 samples of European propolis were tested against wild type and resistant strains of the protozoal pathogens Trypanosoma brucei, Trypanosoma congolense and Leishmania mexicana. the extracts were also tested against Crithidia fasciculata a close relative of Crithidia mellificae, a parasite of bees. Crithidia, Trypanosoma and Leishmania...

Antimicrobial resistant bacteria can become harboured in sediments of post-industrial estuaries. Subsequently, their resistance traits could be enriched by pollutants deposited in the sediments. Recent evidence strongly suggests this may pose hazards that not only affects the health care sector, but could also impact tourism and the aquaculture ind...

Antimicrobial resistance (AMR) represents a major global health threat, as well as a major hazard to sustainable economic development and national security. It remains, therefore, vital that current research aligns to policy development and implementation to alleviate a potential crisis. One must consider, for example, whether drivers of antibiotic...

Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms under...

The protozoan Leishmania mexicana parasite causes chronic non-healing cutaneous lesions in humans and mice with poor parasite control. The mechanisms preventing the development of a protective immune response against this parasite are unclear. Here we provide data demonstrating that parasite sequestration by neutrophils is responsible for disease p...

Autophagy is a central process behind the cellular remodeling that occurs during differentiation of Leishmania, yet the cargo of the protozoan parasite's autophagosome is unknown. We have identified glycosomes, peroxisome-like organelles that uniquely compartmentalize glycolytic and other metabolic enzymes in Leishmania and other kinetoplastid para...

Amino acid utilization is important for the growth of the erythrocytic stages of the human malaria parasite Plasmodium falciparum, however the molecular mechanism that permits survival of the parasite during conditions of limiting amino acid supply is poorly understood. We provide data here suggesting that an autophagy pathway functions in P. falci...

Differentiation of Leishmania life forms is crucial for progression and preadaptation of the parasite to the environmental conditions existing in its hosts. Autophagy is a catabolic degradation process that utilizes cytosolic ATG4s and lysosomal cathepsins to affect protein turnover and remodeling, which are crucial for parasite development, differ...

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory molecule in mammals, which unusually, for a cytokine exhibits tautomerase and oxidoreductase enzymatic activities. Homologues of this well conserved protein are found within diverse phyla including a number of parasitic organisms. Herein, we produced recombinant histidine-tagged Tox...

Macroautophagy in Leishmania, which is important for the cellular remodeling required during differentiation, relies upon the hydrolytic activity of two ATG4 cysteine peptidases (ATG4.1 and ATG4.2). We have investigated the individual contributions of each ATG4 to Leishmania major by generating individual gene deletion mutants (Δatg4.1 and Δatg4.2)...

Comparison of PE species in WT and Δatg5 promastigotes. Negative ion ES-MS survey scans (600–1000 m/z) of lipid extracts with the addition of an internal standard PE (28∶0) from WT (A) and Δatg5 (B) promastigotes. Inserts are ESI-MS-MS positive ion spectra of neutral loss 141 m/z, the internal standard PE (28∶0) is indicated with by IS and an arrow...

Phospholipid species in L. major. Lipids extracted from L. major were analyzed by ES-MS and subjected to MS/MS daughter ion spectra where necessary and assigned structures based upon their fragmentation ions and previous literature characterisations. (DOC)

Plasmids and primers used in this study. (DOC)

Generation and validation of Δatg5. (A) Schematic representation of the ATG5 locus and the plasmid constructs used for gene replacement. Arrows and boxes indicate the ATG5 and antibiotic resistance genes and the 3′ and 5′ flanking DNA sequences, respectively. The restriction enzymes used for the different constructs and the expected sizes of fragme...

Analysis of D3-Ser incorporation into phospholipids in L. major promastigotes. To investigate if the observed increase in PE species in the Δatg5 promastigotes was generated by PS decarboxylase activity, both WT (A) and Δatg5 (B) promastigotes were grown in the presence of D3-serine prior to lipid extraction and analysis by negative ion ES-MS surve...

Author Summary Leishmaniasis is a disease of humans that is of major significance throughout many parts of the world. It is caused by the protozoan parasite Leishmania and mammals are infected through the bite of a sand fly in which the parasite develops. Parasite remodelling crucial for generation of the human-infective forms is aided by the catab...

Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can...

Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can...

Genome mining and biochemical analyses have shown that Leishmania major possesses two pathways for cysteine synthesis--the de novo biosynthesis pathway comprising SAT (serine acetyltransferase) and CS (cysteine synthase) and the RTS (reverse trans-sulfuration) pathway comprising CBS (cystathionine beta-synthase) and CGL (cystathionine gamma-lyase)....

Leishmania major possesses, apparently uniquely, four families of ATG8-like genes, designated ATG8, ATG8A, ATG8B and ATG8C, and 25 genes in total. L. major ATG8 and examples from the ATG8A, ATG8B and ATG8C families are able to complement a Saccharomyces cerevisiae ATG8-deficient strain, indicating functional conservation. Whereas ATG8 has been show...

Leishmania occurs in several developmental forms and thus undergoes complex cell differentiation events during its life-cycle. Those are required to allow the parasite to adapt to the different environmental conditions. The sequencing of the genome of L. major has facilitated the identification of the parasite's vast arsenal of proteolytic enzymes,...

In the past, ultrastructural investigations of Leishmania mexicana amastigotes revealed structures that were tentatively identified as autophagosomes. This study has now provided definitive data that autophagy occurs in the parasite during differentiation both to metacyclic promastigotes and to amastigotes, autophagosomes being particularly numerou...

Cellular remodeling during differentiation is essential for life-cycle progression of many unicellular eukaryotic pathogens such as Leishmania, but the mechanisms involved are largely uncharacterized. The role of endosomal sorting in differentiation was analyzed in Leishmania major by overexpression of a dominant-negative ATPase, VPS4. VPS4(E235Q)...

Leishmania major 3-mercaptopyruvate sulfurtransferase is a crescent-shaped molecule comprising three domains. The N-terminal and central domains are similar to the thiosulfate sulfurtransferase rhodanese and create the active site containing a persulfurated catalytic cysteine (Cys-253) and an inhibitory sulfite coordinated by Arg-74 and Arg-185. A...

Cytosolic 3-mercaptopyruvate sulfurtransferases (EC ) of Leishmania major and Leishmania mexicana have been cloned, expressed as active enzymes in Escherichia coli, and characterized. The leishmanial single-copy genes predict a sulfurtransferase that is structurally peculiar in possessing a C-terminal domain of some 70 amino acids. Homologous genes...

Analysis of diagnoses recorded on under-fives' death certificates in Freetown from 1987 to 1991 revealed that they were attributed thus, acute respiratory infections (ARI); 35%, diarrhoeal diseases (DD); 18%, malaria; 14%, malnutrition; 11%, anaemia; 11%, measles; 9%, prematurity; 7%, convulsions; 6% and tetanus; 3%. Neonates and infants comprised...

A comparison of two studies performed in Sierra Leone on the effect of anthelmintic, chemotherapy, levamisole, albendazole or a placebo in children aged 6 to 10 years on the prevalence and intensity of common soil transmitted helminths (S-THs) infections is presented. In total 501 children were screened, and 394 successfully follow-up. At baseline...