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showing 10 items of 8388 documents
Age reduces resistance and tolerance in malaria-infected mice.
2021
7 pages; International audience; Once infected, hosts can rely on two strategies to cope with parasites: fight them (resist the infection) or minimize the damage they induce (tolerate the infection). While there is evidence that aging reduces resistance, how tolerance varies as hosts become old has been barely studied. Here, we used a rodent malaria parasite (Plasmodium yoelii) to investigate whether 2- and 12-month old house mice differ in their capacity to resist and tolerate the infection. We found that 12-month old mice harbored higher parasitemia, showing that age reduces resistance to malaria. Infection-induced deterioration of host health was assessed using red blood cell and body ma…
Bacterial symbionts in Lepidoptera: Their diversity, transmission, and impact on the host
2018
The insect's microbiota is well acknowledged as a “hidden” player influencing essential insect traits. The gut microbiome of butterflies and moths (Lepidoptera) has been shown to be highly variable between and within species, resulting in a controversy on the functional relevance of gut microbes in this insect order. Here, we aim to (i) review current knowledge on the composition of gut microbial communities across Lepidoptera and (ii) elucidate the drivers of the variability in the lepidopteran gut microbiome and provide an overview on (iii) routes of transfer and (iv) the putative functions of microbes in Lepidoptera. To find out whether Lepidopterans possess a core gut microbiome, we com…
Perils and Promises of Pathogenic Protozoan Extracellular Vesicles
2020
Extracellular vesicles (EVs) are membranous structures formed during biological processes in living organisms. For protozoan parasites, secretion of EVs can occur directly from the parasite organellar compartments and through parasite-infected or antigen-stimulated host cells in response to in vitro and in vivo physiological stressors. These secreted EVs characteristically reflect the biochemical features of their parasitic origin and activating stimuli. Here, we review the species-specific morphology and integrity of parasitic protozoan EVs in concurrence with the origin, functions, and internalization process by recipient cells. The activating stimuli for the secretion of EVs in pathogeni…
Fast-Growing Alveolar Echinococcosis Following Lung Transplantation
2020
International audience; Alveolar echinococcosis is a rare but life-threatening infection caused by the parasiteEchinococcus multilocularis. Its natural history is characterized by a slow parasitic growth over several years. Increased incidence and shorter development delay have been reported in immune-compromised patients. We report the reactivation of aborted lesions within 12 months of lung transplantation leading to a fast-growing aggressive hepatic lesion. Timely identification of alveolar echninococcosis allowed prompt albendazole treatment and radical surgery leading to a favorable outcome 42 months after transplantation. However, close clinical, serological and radiological monitorin…
Diverse relations between ABC transporters and lipids: An overview.
2016
It was first discovered in 1992 that P-glycoprotein (Pgp, ABCB1), an ATP binding cassette (ABC) transporter, can transport phospholipids such as phosphatidylcholine, -ethanolamine and -serine as well as glucosylceramide and glycosphingolipids. Subsequently, many other ABC transporters were identified to act as lipid transporters. For substrate transport by ABC transporters, typically a classic, alternating access model with an ATP-dependent conformational switch between a high and a low affinity substrate binding site is evoked. Transport of small hydrophilic substrates can easily be imagined this way, as the molecule can in principle enter and exit the transporter in the same orientation. …
On the (un)coupling of the chromophore, tongue interactions, and overall conformation in a bacterial phytochrome
2018
Phytochromes are photoreceptors in plants, fungi, and various microorganisms and cycle between metastable red light-absorbing (Pr) and far-red light-absorbing (Pfr) states. Their light responses are thought to follow a conserved structural mechanism that is triggered by isomerization of the chromophore. Downstream structural changes involve refolding of the so-called tongue extension of the phytochrome-specific GAF-related (PHY) domain of the photoreceptor. The tongue is connected to the chromophore by conserved DIP and PRXSF motifs and a conserved tyrosine, but the role of these residues in signal transduction is not clear. Here, we examine the tongue interactions and their interplay with …
Addition of thiols to the double bond of dipeptide C-terminal dehydroalanine as a source of new inhibitors of cathepsin C.
2017
Addition of thiols to double bond of glycyl-dehydroalanine and phenyl-dehydroalanine esters provided micromolar inhibitors of cathepsin C. The structure-activity studies indicated that dipeptides containing N-terminal phenylalanine exhibit higher affinity towards the enzyme. A series of C-terminal S-substituted cysteines are responsible for varying interaction with S1 binding pocket of cathepsin C. Depending on diastereomer these compounds most likely act as slowly reacting substrates or competitive inhibitors. This was proved by TLC analysis of the medium in which interaction of methyl (S)-phenylalanyl-(R,S)-(S-adamantyl)cysteinate (7i) with the enzyme was studied. Molecular modeling enabl…
rbFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences
2018
Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats. Interestingly, rbFOX1 competes with MBNL1 for binding to CCUG expanded repeats and overexpression of rbFOX1 partly releases MBNL1 from sequestration within CCUG RNA foci in DM2 muscle ce…
The hydrolysis of 6-phosphogluconolactone in the second step of pentose phosphate pathway occurs via a two-water mechanism.
2018
Hydrolysis reaction marks the basis of life yet the mechanism of this crucial biochemical reaction is not completely understood. We recently reported the mechanisms of hydrolysis of nucleoside triphosphate and phosphate monoester. These two reactions hydrolyze P-O-P and P-O-C linkages, respectively. Here, we present the mechanism of hydrolysis of δ-6-phosphogluconolactone, which is an important precursor in the second step of the pentose phosphate pathway. Its hydrolysis requires the cleavage of C-O-C linkage and its mechanism is hitherto unknown. We report three mechanisms of hydrolysis of δ-6-phosphogluconolactone based on density functional computations. In the energetically most favorab…
Coordination of the biliverdin D-ring in bacteriophytochromes.
2018
Phytochrome proteins translate light into biochemical signals in plants, fungi and microorganisms. Light cues are absorbed by a bilin chromophore, leading to an isomerization and a rotation of the D-ring. This relays the signal to the protein matrix. A set of amino acids, which is conserved across the phytochrome superfamily, holds the chromophore in the binding pocket. However, the functional role of many of these amino acids is not yet understood. Here, we investigate the hydrogen bonding network which surrounds the D-ring of the chromophore in the resting (Pr) state. We use UV/vis spectroscopy, infrared absorption spectroscopy and X-ray crystallography to compare the photosensory domains…