A Conserved Gene Cluster Rules Anaerobic Oxidative Degradation of
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            -Ornithine

Fonknechten, Nùria; Perret, Alain; Perchat, Nadia; Tricot, Sabine; Lechaplais, Christophe; Vallenet, David; Vergne, Carine; Zaparucha, Anne; Paslier, Denis Le; Weissenbach, Jean; Salanoubat, Marcel

doi:10.1128/jb.01777-08

Cited by 46 publications

(49 citation statements)

References 21 publications

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“…This is a generally favoured pathway by anaerobes, for they can conserve energy without any redox reaction by splitting the deaminated intermediate citrulline by ornithine carbamoyl-phosphate transferase and conserve ATP by carbamate kinase. As expected, C. sticklandii contains all the genes involved in the arginine deiminase pathway as well as the ornithine oxidative and reductive pathways [29,30]. Like C. botulinum and C. sporogenes [34], C. sticklandii possesses an ornithine cyclodeaminase that directly produces proline from ornithine.…”

Section: Resultsmentioning

confidence: 79%

Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence

et al. 2010

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BackgroundClostridium sticklandii belongs to a cluster of non-pathogenic proteolytic clostridia which utilize amino acids as carbon and energy sources. Isolated by T.C. Stadtman in 1954, it has been generally regarded as a "gold mine" for novel biochemical reactions and is used as a model organism for studying metabolic aspects such as the Stickland reaction, coenzyme-B12- and selenium-dependent reactions of amino acids. With the goal of revisiting its carbon, nitrogen, and energy metabolism, and comparing studies with other clostridia, its genome has been sequenced and analyzed.ResultsC. sticklandii is one of the best biochemically studied proteolytic clostridial species. Useful additional information has been obtained from the sequencing and annotation of its genome, which is presented in this paper. Besides, experimental procedures reveal that C. sticklandii degrades amino acids in a preferential and sequential way. The organism prefers threonine, arginine, serine, cysteine, proline, and glycine, whereas glutamate, aspartate and alanine are excreted. Energy conservation is primarily obtained by substrate-level phosphorylation in fermentative pathways. The reactions catalyzed by different ferredoxin oxidoreductases and the exergonic NADH-dependent reduction of crotonyl-CoA point to a possible chemiosmotic energy conservation via the Rnf complex. C. sticklandii possesses both the F-type and V-type ATPases. The discovery of an as yet unrecognized selenoprotein in the D-proline reductase operon suggests a more detailed mechanism for NADH-dependent D-proline reduction. A rather unusual metabolic feature is the presence of genes for all the enzymes involved in two different CO2-fixation pathways: C. sticklandii harbours both the glycine synthase/glycine reductase and the Wood-Ljungdahl pathways. This unusual pathway combination has retrospectively been observed in only four other sequenced microorganisms.ConclusionsAnalysis of the C. sticklandii genome and additional experimental procedures have improved our understanding of anaerobic amino acid degradation. Several specific metabolic features have been detected, some of which are very unusual for anaerobic fermenting bacteria. Comparative genomics has provided the opportunity to study the lifestyle of pathogenic and non-pathogenic clostridial species as well as to elucidate the difference in metabolic features between clostridia and other anaerobes.

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Section: Resultsmentioning

confidence: 79%

Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence

et al. 2010

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“…Rumen fluid samples collected only at 4-hr post-morning feeding were analysed for eight selected microbial populations, and the corresponding pair of primers (forward, reverse) was retrieved from the literature: Ruminococcus flavefaciens (Zhou, McSweeney, Wang, & Liu, 2011); Ruminococcus albus (Zhou et al, 2011); Fibrobacter succinogenes (Zhou et al, 2011); total protozoa (Zhou et al, 2011); total fungi (Zhou et al, 2011); total methanogen (Zhou et al, 2011); Clostridium sticklandii (Fonknechten et al, 2009); Peptostreptococcus anaerobius (Riggio & Lennon, 2002). Total DNA was extracted as described elsewhere (Sharma, John, Damgaard, & McAllister, 2003).…”

Section: Measurements and Analytical Methodsmentioning

confidence: 99%

Effects of dietary Greek oregano (Origanum vulgare ssp. hirtum) supplementation on rumen fermentation, enzyme profile and microbial communities in goats

Paraskevakis

2017

Animal Physiology Nutrition

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This study was conducted to examine in vivo long-term effects of dietary dried oregano (Origanum vulgare ssp. hirtum) whole plant on rumen fermentation, enzyme profile and microbial communities. For this purpose, eight healthy, adult, non-lactating Alpine goats were kept in tie stalls equipped for individual feeding and randomly divided into two homogeneous groups: one fed 0.6 kg of a concentrate mixture and 0.6 kg of wheat straw without any supplementation and served as control group (CON) while the other group (OR) fed the same diet of CON but supplemented with 20 g of dried oregano plants (OPs) to provide daily dosage of 1 ml of essential oil (EO) per animal. The experimental period lasted 69 days and individual rumen fluid samples were obtained every 2 weeks at 0 and 4 hr after feeding. The results showed that dietary supplementation with OPs increased the protease activity (p < .001) and ammonia concentration (p < .05) in the rumen. Among the studied microbial populations, Peptostreptococcus anaerobius (p = .028) and Clostridium sticklandii (p < .001) were found to be the most sensitive to oregano at the current dosage. Furthermore, the total methanogen population significantly decreased (p < .05). It is concluded that a long-term dietary administration of OPs can suppress specific rumen micro-organisms and modify rumen fermentation favourably at least by means of suppressing methanogens.

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“…In this latter category, C. difficile enriched expression of genes converting ornithine to alanine, and constitutively expressed genes converting ornithine to proline (Figs. 3C, S3A), enabling ornithine's use in both oxidative and reductive Stickland reactions (37). These effects cooccurred with CSAR's up-regulation of an arginine deiminase (ADI) fermentation pathway by 20h of C. difficile infection ( Fig.…”

Section: Cbi and Csar Differentially Modulate C Difficile Gene Exprementioning

confidence: 96%

In vivocommensal control ofClostridioides difficilevirulence

Girinathan

DiBenedetto

Worley

et al. 2020

Preprint

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We define multiple mechanisms by which commensals protect against or worsen Clostridioides difficile infection.Using a systems-level approach we show how two species of Clostridia with distinct metabolic capabilities modulate the pathogen's virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenter Clostridium bifermentans survived infection, while colonization with the butyrate-producer, Clostridium sardiniense, more rapidly succumbed. Systematic in vivo analyses revealed how each commensal altered the pathogen's carbon source metabolism, cellular machinery, stress responses, and toxin production. Protective effects were replicated in infected conventional mice receiving C. bifermentans as an oral bacteriotherapeutic that prevented lethal infection. Leveraging a systematic and organism-level approach to host-commensalpathogen interactions in vivo, we lay the groundwork for mechanistically-informed therapies to treat and prevent this disease.Clostridioides difficile, the etiology of pseudomembranous colitis, causes substantantial morbidity, mortality and >$5 billion/year in US healthcare costs. Infections commonly arise after antibiotic disruption of the microbiota, allowing the pathogen to proliferate and release toxins that ADP ribosylate host rho GTPases (1, 2). In patients with recurrent C. difficile infections, fecal microbiota transplant (FMT) has become standard of care to reconstitute the microbiota and prevent recurrence. While intensive efforts to develop defined microbial replacements for FMT have been undertaken, relatively little is known about the molecular, metabolic, and microbiologic mechanisms by which specific members of the microbiota modulate the pathogen's virulence in vivo, information critical for therapeutics development (3,4). Given deaths in immunocompromised patients from drug-resistant pathogens in FMT preparations (5), therapies informed by molecular mechanisms of action among will enable options with improved safety and efficacy (6, 7).C. difficile's pathogenicity locus (PaLoc) contains the tcdA, tcdB and tcdE genes that encode the A and B toxins, and holin involved in toxin export, respectively. tcdR encodes a sigma factor specific for the toxin gene promoters, and the tcdC gene a TcdR anti-sigma factor (8-10). Multiple metabolic regulators influence PaLoc expression (11,12). In particular, C. difficile elaborates toxin under starvation conditions to extract nutrients from the host and promote the shedding of spores.C. difficile, like other cluster XI Clostridia, possesses diverse genetic machinery to utilize different carbon sources for energy and growth. In addition to carbohydrate fermentation, the pathogen uses Stickland fermentations, and Stickland-independent fermentations of other amino acids including threonine and cysteine (13), to extract energy from amino acids. The pathogen can ferment ethanolamine, extract electrons from primary bile salts, and undergo carbon fixation through the Wood-Ljungdhal pathway to generate acetate for metabolism...

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A Conserved Gene Cluster Rules Anaerobic Oxidative Degradation of l -Ornithine

Cited by 46 publications

References 21 publications

Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence

Clostridium sticklandii, a specialist in amino acid degradation:revisiting its metabolism through its genome sequence

Effects of dietary Greek oregano (Origanum vulgare ssp. hirtum) supplementation on rumen fermentation, enzyme profile and microbial communities in goats

In vivocommensal control ofClostridioides difficilevirulence

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