title: Comparative biochemistry of Giardia, Hexamita and Spironucleus: Enigmatic diplomonads.
abstract: The diplomonad genera are here represented by three highly diverse species, both free-living (Hexamita inflata), and parasitic (Spironucleus vortens and Giardia intestinalis). All three are moderately aerotolerant flagellates, inhabiting environments where O2 tensions are low and fluctuating. Many diplomonads are opportunistic pathogens of avian, terrestrial and aquatic animals. Hexamitids inhabit deep waters and sediments of lakes and marine basins, S. vortens commonly infects the intestinal tract of ornamental fish, particularly of cichlids and cyprinids, and G. intestinalis, the upper intestinal tracts of humans as well as domestic and farm animals. Despite these very different habitats, their known physiological and biochemical characteristics are similar, but they do differ in significant respects as their lifestyles and life cycles demand. They have efficient O2 scavenging systems, and are highly effective at countering rapid O2 fluctuations, or clustering away from its source (except for G. intestinalis when attached to the jejunal villi). Their core metabolic pathways (glycolysis using pyrophosphate), incomplete tricarboxylic acid cycle (lacking α-ketoglutarate dehydrogenase), and amino acid metabolism (with an alternative energy-generating arginine dihydrolase pathway as a possibility in some cases), largely conform to those of other protists inhabiting low-O2 environments. Mitochondrial evolutionary reduction to give hydrogenosomes as seen in Spironucleus spp. has proceeded further to its minimal state in the mitosomes of G. intestinalis. Understanding of essential redox reactions and the maintentence of redox state, especially in the infective encysted stage of G. intestinalis provide increasing possibilities for parasite control. To this aim a plethora of new synthetic chemicals and natural products (especially those from garlic, Allium sativum) show promise as replacements for the highly effective (but potentially toxic to higher organisms) 5-nitroimidazoles (e.g., metronidazole) in the treatment and/or prevention of dimplomonad infection in humans and animals.
authors.affiliation: School of Biosciences, Cardiff University, Main Building, Museum Avenue, Cathays Park, Cardiff CF10 3AT, Wales, UK. Electronic address: lloydd@cf.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Lloyd
authors.affiliation: Cultech Ltd., Unit 3, Christchurch Road, Baglan Industrial Park, Port Talbot, West Glamorgan, SA12 7BZ Wales, UK.
authors.forename: Catrin F
authors.initials: CF
authors.lastname: Williams
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D016828:Diplomonadida / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D023281:Genomics; D005872:Giardia / Q000145:classification / Q000187:drug effects / Q000502:physiology; D008018:Life Cycle Stages; D015388:Organelles / Q000378:metabolism; D010802:Phylogeny; D011528:Protozoan Infections / Q000188:drug therapy / Q000378:metabolism* / Q000469:parasitology*
chemical_list: D000981:Antiprotozoal Agents
keywords: 5-Nitroimidazoles; Cytoskeleton; Encystment; Hydrogenosomes; Mitosomes; Oxygen scavenging