Uric acid, the final product of purine metabolism in humans, accumulates in blood and tissues at relatively high concentrations1 as humans lack the enzyme uricase2,3. Under inflammatory conditions, uric acid can be oxidised to yield reactive intermediates4. In activated neutrophils, myeloperoxidase (MPO) catalyses the oxidation of uric acid by hydrogen peroxide, leading to the formation of urate hydroperoxide (UH)5,6. While recent studies have shown that UH is toxic to bacteria lacking peroxiredoxins7, its precise mechanism of toxicity and the existence of dedicated bacterial defence systems remain unknown. Here, we identify HiuH as a periplasmic enzyme, conserved across E. coli strains, that specifically degrades UH. Our findings reveal that UH selectively induces the expression of hiuH and that HiuH efficiently detoxifies UH both in vitro and in bacterial cells. HiuH cooperates with MsrP, a periplasmic methionine sulfoxide reductase that repairs UH-induced protein-bound methionine oxidation. This combined defence offering both direct detoxification and damage repair, is essential for bacterial survival under UH stress, and confers a competitive fitness advantage in a DSS-induced mouse model of colitis. Although UH is chemically transient, our work shows that it imposes durable biological consequences and a sufficient fitness cost in the in vivo niches occupied by E. coli to favour the evolution of a dedicated detoxification pathway beyond general oxidative-stress responses, defining a key adaptation to periods of gut inflammation.

Despite continuous progress made on the taxonomy of the genus Tropidophorus,the Lao Water Skink,T.laotus,is only known from brief descriptions of its syntypes in historical literature.Here we designate a lectotype and paralectotype of the species,redescribe the species based on the type series and newly collected topotypes,provide the first colored photographs of taxonomically-verified individuals,and estimate its phylogenetic position using mitochondrial DNA data for the first time.Using these comparable data,we confirm that the previously identified"T.berdmorei"population from southern Yunnan Province,China,represents a distinct new species that is closely related and morphologically similar to T.laotus,but differs from true T.laotus by having considerable genetic divergence(4.7%-4.8%for 12S,3.2%-4.2%for 16S)and distinct morphological characters(e.g.,undivided frontonasal scales and a distinct color pattern of the throat).The southern Yunnan population is therefore described as a new species.With the above newly acquired data,we update the checklist and the provincial-level distribution of the genus Tropidophorus in China and compile an updated key to all recognized species of the genus from China and Indochina.

The Saharo-Sindic desert, the world largest arid region, is often treated as having low alpha and beta diversity of reptiles. However, the region is, in general, poorly studied and its biodiversity is likely to be grossly underestimated. Among the species in this region, the Telescopus dhara-obtusus complex has the widest distribution, a long history of controversial species definition, and unstable taxonomic status. We analysed 27 meristic characters, 19 measurements, and 35 osteological characters of this species complex by examining 282 specimens. We also analysed intra- and interspecific genetic structure and differentiation using five mitochondrial and two nuclear genes from 40 specimens. Our results reveal the T. dhara-obtusus complex as paraphyletic, comprising two major species groups: the T. dhara group and the T. obtusus group. The T. dhara group has eight species: T. dhara, T. guentheri (revalidated), T. pulcher, and five new species. The T. obtusus group is formed by 12 species: T. obtusus, T. somalicus, T. tripolitanus, T. variegatus, T. semiannulatus, T. beetzi, T. finkeldeyi, T. gezirae, and four new species. We describe all new taxa, redescribe the senior ones, and provide the first detailed description of a skull for the genus. The total number of species of Telescopus increases from 14 to 25.

Documenting intra-specific diet variations among remote populations, thus across different habitats, is important to address evolutionary (e.g., phenotypic plasticity) and conservation issues (e.g., capacity to adapt to changing prey availability). We compared the diet of different populations of Asp vipers ( Vipera aspis aspis ; Linnaeus, 1758) living in contrasted habitats of France and Switzerland. We sampled 1680 individuals in five geographical areas, broadly encompassing the distribution range of the species (West to East and North to South): Group 1 = Western Central France; Group 2 = Central France; Group 3 = West France; Group 4 = South France, and Group 5 = Switzerland. We compared mean total body size (TL) of snakes and their diet. We found strong similarities among the groups with a predominance of micromammals in the diet. In mountainous area (Group 5), however, snakes included a substantial number of reptiles and fed occasionally on amphibians and birds. The diet varied ontogenetically (juveniles often consuming lizards, adults heavily feeding on mammals) and sexually (females tending to feed more extensively on mammals). Overall, our results suggest that Asp vipers maintain a diet largely based on micromammals (mostly voles), at least across their continental distribution range.

Bioinspired from cationic antimicrobial peptides, sequence-defined triazolium-grafted peptoid oligomers (6- to 12-mer) were designed to adopt an amphipathic helical polyproline I-type structure. Their evaluation on a panel of bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis), pathogenic fungi (Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus), and human cells (hRBC, BEAS-2B, Caco-2, HaCaT, and HepG2) enabled the identification of two heptamers with improved activity to selectively fight Staphylococcus aureus pathogens. Modulation of parameters such as the nature of the triazolium and hydrophobic/lipophilic side chains, the charge content, and the sequence length drastically potentiates activity and selectivity. Besides, the ability to block the proinflammatory effect induced by lipopolysaccharide or lipoteichoic acid was also explored. Finally, biophysical studies by circular dichroism and fluorescence spectroscopies strongly supported that the bactericidal effect of these triazolium-grafted oligomers was primarily due to the selective disruption of the bacterial membrane.

Microbial communities are found throughout the biosphere, from human guts to glaciers, from soil to activated sludge. Understanding the statistical properties of such diverse communities can pave the way to elucidate the common mechanisms ...Multiple ecological forces act together to shape the composition of microbial communities. Phyloecology approaches—which combine phylogenetic relationships between species with community ecology—have the potential to disentangle such forces but are often ...

The mixed quality evidence about non-front-fanged snake bites has included unsupported speculation and presumption; the possible role of atopy and/or primary hypersensitivity have often been prematurely discounted. Described is a medically insignificant bite by a captive African emerald snake, Hapsidophrys smaragdinus Schlegel, 1837 (Colubridae, Colubrinae) that caused the development of moderate Type IV hypersensitivity; the 44-year-old male victim experienced persistent pruritis and an erythematous bite site maculopapular dermatitis that slowly resolved and required 6 days for full resolution. The victim had received several previous medically insignificant bites from non-front-fanged snakes. Brief comparison is made with a previously reported case consistent with a mixed clinical picture of local mild envenoming and hypersensitivity from a bite by another colubrine, the coin snake (Hemmorhois nummifer). This case highlights slowly accumulating evidence supporting the risk of acquired and primary hypersensitivity to some snakebites in susceptible individuals. In order to provide accurate medical risk profiles for less-known snake species it is essential that the case of any patient developing acute or delayed effects from bites by these species is formally documented. The need for further attention to atopic risks, especially in private collectors, is emphasised with consideration of venom/other ophidian product-induced anaphylaxis.

Here we report two antimicrobial peptides (AMPs), HG2 and HG4 identified from a rumen microbiome metagenomic dataset, with activity against multidrug-resistant (MDR) bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) strains, a major hospital and community-acquired pathogen. We employed the classifier model design to analyse, visualise, and interpret AMP activities. This approach allowed in silico discrimination of promising lead AMP candidates for experimental evaluation. The lead AMPs, HG2 and HG4, are fast-acting and show anti-biofilm and anti-inflammatory activities in vitro and demonstrated little toxicity to human primary cell lines. The peptides were effective in vivo within a Galleria mellonella model of MRSA USA300 infection. In terms of mechanism of action, HG2 and HG4 appear to interact with the cytoplasmic membrane of target cells and may inhibit other cellular processes, whilst preferentially binding to bacterial lipids over human cell lipids. Therefore, these AMPs may offer additional therapeutic templates for MDR bacterial infections.

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.

The reaction pathways were investigated by which a fungoid chitosan (CsG) may protect against photooxidative decay of model solutions and a sulphite-free white wine. Samples containing CsG were dark incubated for 2 days before exposure to fluorescent lighting for up to 21 days in the presence of wine like (+)-catechin and/or iron doses. In both systems CsG at winemaking doses significantly reduced the photoproduction of acetaldehyde and, to a better extent, glyoxylic acid, two key reactive aldehydes implicated in wine oxidative spoilage. After 21 days, CsG was two-fold more effective than sulphur dioxide in preventing glyoxylic acid formation and minimizing the browning of white wine. Among the antioxidant mechanisms involved in CsG protective effect, iron chelation, and hydrogen peroxide quenching were demonstrated. Besides, the previously unreported tartrate displacement from the [iron(III)-tartrate] complex was revealed as an additional inhibitory mechanism of CsG under photo-Fenton oxidation conditions.

The first reported snakebite by an African snake-eater, Polemon spp. (Atractaspididae, Aparallactinae); Local envenoming by Reinhardt's snake-eater, Polemon acanthias (Reinhardt, 1860). Toxicon XX, xxx. A 51-yr-old male herpetologist was bitten on the left index finger by a captive male Polemon acanthias while manually removing fragments of incompletely shed skin from the specimen. The snake sustained its bite for approximately 2 mins, advancing its jaws several times. The victim rapidly developed moderate pain, erythema, progressive edema that ultimately extended to the left wrist; a blister later developed in the wound site, as well as joint stiffness in the bitten and adjacent two fingers that limited flexion and extension. These effects regressed during the week following the bite, but recurred thereafter and were similar to the effects that developed immediately post-envenoming. There were no systemic signs or symptoms. The victim sought medical advice and was treated with broad-spectrum antibiotics, antihistamines and wound care; no laboratory investigations were conducted. He improved during the subsequent month with complete resolution in 5 and one-half weeks. This is the first documented bite by a Polemon spp. and the victim's clinical course suggests the development of local effects from venom components. The phylogenetic relationship of Polemon spp. with the burrowing asps (Atractaspis spp.) and the similarity of some of the features of this local envenoming by P. acanthias with mild/moderate envenoming by some Atractaspis spp., suggests that none of these snakes should be handled; they should be considered capable of inflicting potentially serious envenoming.

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.

La liste taxinomique est etablie pour les Serpents des Petites Antilles. Elle tient compte des publications les plus recentes. A cote du nom scientifique zoologique, un nom scientifique francais est joint a chaque taxon. La presence passee des Boa et des Clelia dans les Petites Antilles est clarifiee et discutee. Il n’y a pas eu de Bothrops dans les Grenadines. Les Petites Antilles ne forment pas une aire biogeographique homogene.

Snakebite envenoming is a relevant public health problem in French Guiana, and Bothrops atrox is responsible for the vast majority of envenomings in this overseas French territory. The preclinical efficacy of freeze-dried antivenoms manufactured in Costa Rica (Polival-ICP®) and Mexico (Antivipmyn Tri®) was assessed against the lethal, hemorrhagic, in vitro coagulant, and myotoxic effects of Bothrops atrox venom from French Guiana. Antivenoms differ in protein concentration and in the type of active principle (IgG and F (ab')2, respectively). Polival-ICP® showed significantly higher neutralizing activity against lethal, hemorrhagic and in vitro coagulant activities of the venom. Antivenoms neutralized myotoxic effect to a similar extent. In the case of lethal activity, Antivipmyn Tri® did not neutralize the effect at the highest antivenom level tested (1 mg venom/mL antivenom).

Plant α-galactosides belonging to the raffinose family oligosaccharides (RFOs) and considered as prebiotics, are commonly degraded by α-galactosidases produced by the human gut microbiome. In this environment, the Ruminococcus gnavus E1 symbiont–well-known for various benefit–is able to produce an original RgAgaSK bifunctional enzyme. This enzyme contains an hydrolytic α-galactosidase domain linked to an ATP dependent extra-domain, specifically involved in the α-galactoside hydrolysis and the phosphorylation of the glucose, respectively. However, the multi-modular relationships between both catalytic domains remained hitherto unexplored and has been, consequently, herein investigated. Biochemical characterization of heterologously expressed enzymes either in full-form or in separated domains revealed similar kinetic parameters. These results were supported by molecular modeling studies performed on the whole enzyme in complex with different RFOs. Further enzymatic analysis associated with kinetic degradation of various substrates followed by high pressure anionic exchange chromatography revealed that catalytic efficiency decreased as the number of D-galactosyl moieties branched onto the oligosaccharide increased, suggesting a preference of RgAgaSK for RFO’s short chains. A wide prevalence and abundance study on a human metagenomic library showed a high prevalence of the RgAgaSK encoding gene whatever the health status of the individuals. Finally, phylogeny and synteny studies suggested a limited spread by horizontal transfer of the clusters’ containing RgAgaSK to only few species of Firmicutes, highlighting the importance of these undispersed tandem activities in the human gut microbiome.

The combination of increased incidence of drug-resistant strains of bacteria and a lack of novel drugs in development creates an urgency for the search for new antimicrobials. Initial screening of compounds from an in-house library identified two 6-bromoindolglyoxylamide polyamine derivatives (3 and 4) that exhibited intrinsic antimicrobial activity towards Gram-positive bacteria, Staphylococcus aureus and S. intermedius with polyamine 3 also displaying in vitro antibiotic enhancing properties against the resistant Gram-negative bacterium Pseudomonas aeruginosa. A series of 6-bromo derivatives (5-15) were prepared and biologically evaluated, identifying analogues with enhanced antibacterial activity towards Escherichia coli and with moderate to excellent antifungal properties. Polyamine 3, which includes a spermine chain, was the most potent of the series - its mechanism of action was attributed to rapid membrane permeabilization and depolarization in both Gram-positive and Gram-negative bacteria.

Despite the fact that venom is an intrinsically ecological trait, the ecological perspective has been widely neglected in toxinological research. This neglect has hindered our understanding of the evolution of venom by causing us to ignore the interactions which shape this evolution, interactions that take place between venomous snakes and their prey and predators, as well as among conspecific venomous snakes within populations. In this opinion piece, we introduce and briefly discuss several ecologically oriented concepts that may be of interest to toxinologists, before reviewing a range of non-front-fanged snake taxa that have been neglected toxinologically, but which represent the majority of extant ecological diversity amongst snakes. We conclude by noting that the ecological perspective even has something to offer to clinical toxinology, in the wake of the World Health Organization reinstating snakebite envenoming to its list of Neglected Tropical Diseases.

A series of substituted di-indolglyoxylamido-spermine analogues were prepared and evaluated for intrinsic antimicrobial properties and the ability to enhance antibiotic action. As a compound class, intrinsic activity was typically observed towards Gram-positive bacteria and the fungus Cryptococcus neoformans, with notable exceptions being the 5-bromo- and 6-chloro-indole analogues which also exhibited modest activity (MIC 34-50 mu M) towards the Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae. Several analogues enhanced the activity of doxycycline towards the Gram-negative bacteria Pseudomonas aeruginosa, E. coli, K. pneumoniae and Acinetobacter baumannii. Of particular note was the identification of five antibiotic enhancing analogues (5-Br, 7-F, 5-Me, 7-Me, 7-Me) which also exhibited low to no cytotoxicity and red blood cell haemolytic properties. The mechanisms of action of the 5-Br and 7-F analogues were attributed to the ability to disrupt the integrity of, and depolarize, bacterial membranes. (C) 2019 Elsevier Masson SAS. All rights reserved.