Molecular & Biochemical Parasitology 197 (2014) 43–49

Contents lists available at ScienceDirect

Molecular & Biochemical Parasitology

Review

Comparative biochemistry of , Hexamita and :

Enigmatic

a,∗ b

David Lloyd , Catrin F. Williams

a

School of Biosciences, Cardiff University, Main Building, Museum Avenue, Cathays Park, Cardiff CF10 3AT, Wales, UK

b

Cultech Ltd., Unit 3, Christchurch Road, Baglan Industrial Park, Port Talbot, West Glamorgan, SA12 7BZ Wales, UK

a r a

t b

i c s t

l e i n f o r a c t

Article history: The genera are here represented by three highly diverse species, both free-living (Hexamita

Received 30 July 2014

inflata), and parasitic (Spironucleus vortens and Giardia intestinalis). All three are moderately aerotolerant

Received in revised form 3 October 2014

flagellates, inhabiting environments where O2 tensions are low and fluctuating. Many diplomonads are

Accepted 3 October 2014

opportunistic pathogens of avian, terrestrial and aquatic animals. Hexamitids inhabit deep waters and

Available online 16 October 2014

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

Keywords:

as domestic and farm animals. Despite these very different habitats, their known physiological and bio-

Cytoskeleton

Hydrogenosomes chemical characteristics are similar, but they do differ in significant respects as their lifestyles and life

Mitosomes cycles demand. They have efficient O2 scavenging systems, and are highly effective at countering rapid

Oxygen scavenging O2 fluctuations, or clustering away from its source (except for G. intestinalis when attached to the jeju-

Encystment nal villi). Their core metabolic pathways (glycolysis using pyrophosphate), incomplete tricarboxylic acid

5-Nitroimidazoles cycle (lacking ␣-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 infec-

tive 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.

© 2014 Elsevier B.V. All rights reserved.

Contents

1. Introduction: phylogeny, morphology, genomics and life cycles ...... 44

2. Cytoskeletal components ...... 44

3. Organelles and vesicles ...... 44

4. Central metabolism ...... 45

5. Encystment ...... 45

6. Chemotherapeutic intervention and potential target sites ...... 46

Acknowledgements ...... 48

Appendix A. Diplomonads: both harmless free-living protozoa and important parasites ...... 48

References ...... 48

∗

Corresponding author.

E-mail address: [email protected] (D. Lloyd).

http://dx.doi.org/10.1016/j.molbiopara.2014.10.002

0166-6851/© 2014 Elsevier B.V. All rights reserved.

44 D. Lloyd, C.F. Williams / Molecular & Biochemical Parasitology 197 (2014) 43–49

1. Introduction: phylogeny, morphology, genomics and life segregation, organelle transport, endocytosis, maintenance of cell

cycles shape and cyto-differentiation between life cycle stages. However,

Giardia spp. have the most divergent actin of any known ,

The diplomonads (suborder Diplomonadida, family Hexamiti- a characteristic that may be regarded as an indicator of its early-

dae) are a group of aerotolerant anaerobic flagellates, which possess branching status [16]. It has more than 80 putative actin-binding

a double set of cellular organelles. Amongst the diplomonad genera proteins, many of which are highly conserved and thus indis-

are Hexamita, Giardia and Spironucleus [1,2]. Species of Hexamita pensably representing the earliest functions of the cytoskeleton,

are mostly free-living organisms that reside in anaerobic water concerned with nucleus and flagella [17]. Microtubule dynamics in

sediments [3], whereas the other taxa are almost exclusively para- Giardia spp. are regulated by end-tracking and end-binding pro-

sites, which commonly inhabit the intestinal tract of mammals, teins, e.g., for segregation of nuclear envelopes, median bodies and

birds, reptiles, amphibians and fish [4–9]. Diplomonads are mem- mitotic spindles.

bers of the super-group of protista defined by an asymmetric The distinctive specialized giardial features are the ventral disc,

feeding groove excavated from one side and hence termed the a spiral microtubule array constructed from 50 parallel micro-

“”. They are thus flagellated that are taxono- tubules, and associated micro-ribbons and lateral crest [18]. These

mically related to the and . Discussion still act together to form a structure capable of forming a continu-

revolves about their ‘primitive status’, i.e., whether they are early- ous attachment seal with the jejunal epithelium of the host and

branching eukaryotes, or crown taxa. They are characterized by have at least 18 unique proteins [19]. Flagellar proteins include the

␣

their possession of two haploid nuclei, each associated with four canonical - and ␤-tubulins, but also 10 metabolic enzymes, and

flagella. In Spironucleus spp. the paired nuclei taper anteriorly and Giardia-specific cytoskeletal elements (6 distinct giardins) [20]. One

are wrapped around each other at their apices, forming an S-shape of these, ␣-11-giardin, is located mainly in the plasma membranes

when viewed in transverse section of the anterior end of the cell. and basal bodies of the anterior flagella [20]. In G. intestinalis the

In other diplomonads the exact shape and location of nuclei are anterior flagella are mainly responsible for fine control over steer-

diagnostic for genus [2]. ing whereas the ventral flagella are used for turning and navigation

Three genes (SSUrRNA, ␣-tubulin and HSP90) selected to of propulsion [21].

explore the phylogenetic relationship between diplomonads

and other members of the group Fornicata (mononucleate

enteromonads, and ) suggests that 3. Organelles and vesicles

the diplokaryotic condition arose several times independently, or

that secondary reduction gave rise on several occasions to the Membranous inclusions in diplomonads, as described in a

monokaryotic enteromonads. Thus neither the internal phylogeny pioneering series of electron microscopy studies [1], have only

nor the positions on the eukaryotic tree are resolved [10]. A variant recently been functionally characterized, and even now the rich

genetic code [11] (postulated to be more robust to error [12]) in diversities of membranes, redox-active organelles, vesicles, and

which TAA and TAG encode glutamine rather than the usual ter- storage granules have not been separated and completely bio-

mination codon is utilized by almost all diplomonads, but with chemically defined. Redox-active organelles in diplomonads are

the genus Giardia alone using the universal genetic code [11,12]. the products of reductive evolutionary loss of mitochondrial con-

Both nuclei in G. intestinalis are transcriptionally active, and unusual stituents [22–24]: this has involved losses of respiratory chain

cysteine-rich structural proteins (variable surface and high cysteine components and associated ATP synthase and acquisition of both

membrane proteins, VSP and HCMPs) are the single largest class bacterial and archaeal proteins. In G. intestinalis this process has

of products [13]. These are concerned with host specificities and been taken to its extremes and the resulting mitosomes [25] have

antigenic functions and show strain differences [14]. Also promi- been so extensively structurally modified that they are hardly

nent are protein kinases (cell cycle control serine-threonine (NEK) recognizable as being mitochondria-derived. Whereas mitochon-

kinases) with inferred signalling functions, and laterally transferred dria typically possess >1500 proteins, fractions containing these

genes from both archaea and eubacteria [13,14]. Of the 5012 pro- 150 nm double-membrane bounded organelles have only 20 con-

tein coding genes identified in Giardia, most are conserved between firmed mitosomal proteins, 9 of which are components of FeS

all three sequenced strains, although the extent of chromosomal cluster assembly machinery [26]. Their inner membrane has no

rearrangements across all chromosomes was unexpected. detectable transmembrane electrochemical potential [27], and nei-

The genome of S. salmonicida (≈12.9 Mbp; 8067 annotated ther hydrogenase nor pyruvate: ferredoxin oxidoreductase locate

protein-coding genes), is different from that of the haploid genome to subcellular fractions containing the mitosomes. Their only

of G. intestinalis (∼11.7 Mbp; 5012 protein-coding genes) in that known function is the maturation and scaffold assembly of FeS

promoter-like motifs were found upstream of expressed genes, clusters necessary for redox proteins [28]. These vesicles possess

inferring a more delicate regulation of transcription [15]. Cysteine- many but not all of the complex membrane transport functions

rich membrane protein codons abound in both diplomonad characteristic of the inner and outer membranes of mitochon-

genomes, and several cyst-wall proteins are common to both. All dria [29]. Electron transport and generation of electrochemical

the enzymes involved in the synthesis of GalNAAc in the Giardia potential occur in Giardia in specialized areas of the plasma mem-

cyst wall can also be found in S. salmonicida. However, the extended brane [30], and subcellular fractionation reveals sedimentable

putative metabolic, bioenergetic, and antioxidant protective reper- vesicle-associated NAD(P)H dehydrogenases and pyruvate: ferre-

toire of this fish parasite is much more elaborate. This suggests that, doxin oxidoreductase [31].

although both these organisms must pass through an encysted state In the two species of Spironucleus studied, S. salmonicida and

during their life cycles, the requirement for adaptation to tissue S. vortens, the major redox active organelles are hydrogenosomes,

invasiveness in the fish is more highly developed. much larger (>500 nm) and more highly organized than mito-

somes, and still structurally recognizable as being mitochondrial

descendents. Rich in flavoproteins [15,23], including presumably

2. Cytoskeletal components the flavodiiron protein terminal oxidase responsible for O2 scav-

enging [32], the most prominent metabolic characteristic is the

In common with many eukaryotes all diplomonads have diverse copious cyanide-, CO-, and metronidazole-sensitive generation of

microtubule arrays involved in motility, cytokinesis, chromosome dihydrogen gas indicative of an Fe-only hydrogenase [33]. This Download English Version: https://daneshyari.com/en/article/5915402

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