Bulky Trichomonad Genomes: Encoding a Swiss Army Knife

Barratt, Joel; Gough, Rory; Stark, Damien; Ellis, John

doi:10.1016/j.pt.2016.05.014

Cited by 16 publications

(13 citation statements)

References 96 publications

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“…We demonstrated a key role for dietary fiber in enabling Tritrichomonas colonization, which could be met by inulin but not cellulose, suggesting similar dietary functions as shown in termite parabasalid symbionts, which are critical for digestion of complex carbohydrates like lignocellulose (Brune, 2014). The capacity of Tritrichomonas to degrade recalcitrant complex polysaccharides is consistent with genomic replication of glycolytic enzymes (Barratt et al, 2016) and fermentative metabolism culminating in metabolic end-products of the mitochrondria-like hydrogenosomes, including acetate, succinate and hydrogen (Muller et al, 2012). Notably, other eukaryotic pathosymbionts, including helminths, share similar metabolic pathways (Muller et al, 2012).…”

Section: Discussionmentioning

confidence: 74%

A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling

Schneider

O’Leary

Moltke

et al. 2018

Cell

365

390

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SUMMARY The small intestinal tuft cell-ILC2 circuit mediates epithelial responses to intestinal helminths and protists by tuft cell chemosensory-like sensing and IL-25-mediated activation of lamina propria ILC2s. Small intestine ILC2s constitutively express the IL-25 receptor, which is negatively regulated by A20 (Tnfaip3). A20-deficiency in ILC2s spontaneously triggers the circuit, and, unexpectedly, promotes adaptive small intestinal lengthening and remodeling. Circuit activation occurs upon weaning, and is enabled by dietary polysaccharides that render mice permissive for Tritrichomonas colonization, resulting in luminal accumulation of acetate and succinate, metabolites of the protist hydrogenosome. Tuft cells express GPR91, the succinate receptor, and dietary succinate, but not acetate, activates ILC2s via a tuft-, TRPM5-, and IL-25-dependent pathway. Also induced by parasitic helminths, circuit activation and small intestinal remodeling impairs infestation by new helminths, consistent with the phenomenon of concomitant immunity. We describe a metabolic sensing circuit that may have evolved to facilitate mutualistic responses to luminal pathosymbionts.

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Section: Discussionmentioning

confidence: 74%

A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling

Schneider

O’Leary

Moltke

et al. 2018

Cell

365

390

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“…Considering the predicted genome sizes [22], there is no apparent correlation between these and the number of expressed genes. The data add additional credit to the dynamic and expanded nature of the genomes this protist group is known for [21, 59].…”

Section: Resultsmentioning

confidence: 99%

Characterization of the BspA and Pmp protein family of trichomonads

et al. 2019

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Background Trichomonas vaginalis is a human-infecting trichomonad and as such the best studied and the only for which the full genome sequence is available considering its parasitic lifestyle, T. vaginalis encodes an unusually high number of proteins. Many gene families are massively expanded and some genes are speculated to have been acquired from prokaryotic sources. Among the latter are two gene families that harbour domains which share similarity with proteins of Bacteroidales/Spirochaetales and Chlamydiales: the BspA and the Pmp proteins, respectively. Results We sequenced the transcriptomes of five trichomonad species and screened for the presence of BspA and Pmp domain-containing proteins and characterized individual candidate proteins from both families in T. vaginalis . Here, we demonstrate that (i) BspA and Pmp domain-containing proteins are universal to trichomonads, but specifically expanded in T. vaginalis ; (ii) in line with a concurrent expansion of the endocytic machinery, there is a high number of BspA and Pmp proteins which carry C-terminal endocytic motifs; and (iii) both families traffic through the ER and have the ability to increase adhesion performance in a non-virulent T. vaginalis strain and Tetratrichomonas gallinarum by a so far unknown mechanism. Conclusions Our results initiate the functional characterization of these two broadly distributed protein families and help to better understand the origin and evolution of BspA and Pmp domains in trichomonads. Electronic supplementary material The online version of this article (10.1186/s13071-019-3660-z) contains supplementary material, which is available to authorized users.

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“…As a consequence, clinical resistance in those parasites has been purported to be rare. It is tempting to speculate in the case of T. vaginalis that due to its “Swiss army knife” of a genome, which shows highly duplicated gene families that may bestow the parasite with extraordinary versatility (Barratt et al 2016), it is able to establish drug resistant infections because of being able to easily compensate for fitness costs. While the details of these mechanisms and their fitness costs should be further explored, we provide here a first insight into adaptation of the unicellular eukaryote T. vaginalis .…”

Section: Discussionmentioning

confidence: 99%

Genetic Indicators of Drug Resistance in the Highly Repetitive Genome of Trichomonas vaginalis

Bradić

Warring

Tooley

et al. 2017

Genome Biology and Evolution

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Trichomonas vaginalis, the most common nonviral sexually transmitted parasite, causes ∼283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance. Reduced representation genome sequencing of ∼100 T. vaginalis clinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium was found to decay rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in genes for which no function has yet been assigned, as well as in functionally-characterized genes relevant to drug resistance (e.g., pyruvate:ferredoxin oxidoreductase). Transcription profiles of resistant strains showed common changes in genes involved in drug activation (e.g., flavin reductase), accumulation (e.g., multidrug resistance pump), and detoxification (e.g., nitroreductase). Finally, we identified convergent genetic changes in lab-derived resistant lines of Tritrichomonas foetus, a distantly related species that causes venereal disease in cattle. Shared genetic changes within and between T. vaginalis and Tr. foetus parasites suggest conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool.

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Bulky Trichomonad Genomes: Encoding a Swiss Army Knife

Cited by 16 publications

References 96 publications

A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling

A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling

Characterization of the BspA and Pmp protein family of trichomonads

Genetic Indicators of Drug Resistance in the Highly Repetitive Genome of Trichomonas vaginalis

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