Éditeur(s) : HAL CCSD
Résumé : International audience
The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falcip-arum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P. falciparum including chloroquine-resistant isolates. Herein we have studied the antimalarial activities of dyes with different scaffold and we report that the triar-ylmethane dye (TRAM) Brilliant green inhibits the growth of asexual stages (IC 50 2 mM) and has exflagellation-blocking activity (IC 50 800 nM) against P. falciparum reference strains (3D7, 7G8) and chloroquine-resistant clinical isolate (Q206). In a second step we have investigated the antiplasmodial activities of two polysulfonated triarylmethane food dyes. Green S (E142) is weakly active against P. falciparum asexual stage (IC 50 x 17 mM) whereas Patent Blue V (E131) is inactive in both antimalarial assays. By applying liquid chromatography techniques for the culture supernatant analysis after cell washings and lysis, we report the detection of Brilliant green in erythrocytes, the selective uptake of Green S (E142) by infected erythrocytes, whereas Patent Blue V (E131) could not be detected within non-infected and 3D7-infected erythrocytes. Overall, our results suggest that two polysulfonated food dyes might display different affinity with transporters or channels on infected RBC membrane.
International journal for parasitology. Drugs and drug resistance

Droits : http://creativecommons.org/licenses/by-nc-sa/
pasteur-01614675
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01614675/file/Leba%20LJ-article%20colorant-version%20publiee.pdf
DOI : 10.1016/j.ijpddr.2017.07.002

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Challenging evaluation of tropical forest biodiversity requires the reporting of taxonomic diversity but also the systematic characterization of wood properties in order to discover new promising species for timber industry. Among wood properties, the dimensional stability is regarded as a major technological characteristic to validate whether a wood species is adapted to commercial uses. Cell structure and organization are known to influence the drying shrinkage making wood density and microfibrils angle markers of choice to predict wood dimensional stability. On the contrary the role of wood extractive content remains unclear. This work focuses on the fast-growing tropical species Bagassa guianensis and we report herein a correlation between heartwood drying shrinkage and extractive content. Chemical extractions and shrinkage experiments were performed on separate wood twin samples to better evaluate correctly how secondary metabolites influence the wood shrinkage behaviour. Extractive content were qualitatively and quantitatively analysed using HPLC and NMR spectroscopy. We found that B guianensis heartwood has a homogeneous low shrinkage along its radius that could not be explained only by its basic density. In fact the low drying shrinkage is correlated to the high extractive content and a corrected model to improve the prediction of wood dimensional stability is presented. Additionally NMR experiments conducted on sapwood and heartwood extracts demonstrate that secondary metabolites biosynthesis occurs in sapwood thus revealing B. guianensis as a Juglans-Type heartwood formation. This work demonstrates that B. guianensis, a fast-growing species associated with high durability and high dimensional stability, is a good candidate for lumber production and commercial purposes.
ISSN: 1932-6203

hal-01392725
https://hal.archives-ouvertes.fr/hal-01392725
https://hal.archives-ouvertes.fr/hal-01392725/document
https://hal.archives-ouvertes.fr/hal-01392725/file/2016_BossuBeaucheneEstevezDuplaisClair_PlosOne_WoodDimentionalStabilityAndSecondaryMetabolites.pdf
DOI : 10.1371/journal.pone.0150777.s005

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : Three new monoterpene indole alkaloids (13) have been isolated from the bark of Geissospermum laeve-, together with the known alkaloids (-)-leuconolam (4), geissolosimine (5), and geissospermine (6). The structures of 1-3 were elucidated by analysis of their HRMS and NMR spectroscopic data. The absolute configuration of geissolaevine (I). was deduced from the comparison of experimental and theoretically calculated ECD spectra. The isolation workflow was guided by a molecular networking-based dereplication strategy using an in-house database of monoterpene indole alkaloids. In addition, five known compounds previously undescribed in the Geissospermum genus were dereplicated from the G. laeve alkaloid extract network and were assigned with various levels of identification confidence. The antiparasitic activities against Plasmodium falciparum and Leishmania donovani as well as the Ortotoxic activity against the MRC-5 cell line were determined for compounds 1-5.
ISSN: 0163-3864

hal-01605065
https://hal.archives-ouvertes.fr/hal-01605065
DOI : 10.1021/acs.jnatprod.6b01013
PRODINRA : 402605
PUBMED : 28282127

Éditeur(s) : HAL CCSD
Résumé : The bacterial microbiota of ants (Hymenoptera: Formicidae) is known to have a defensive role in social insects, particularly for leaf-cutting ants (Formicidae: Attini) due to the use of antimicrobial molecules produced by cuticular actinobacteria. In this thesis, we studied the bacterial microbiota of ants in French Guyana using different approaches based on natural products chemistry and molecular ecology. The first chapter describes the isolation, identification, culture and biological evaluations of 43 cuticular actinobacteria. Antagonism bioassays of isolated strains and antibiotic activities of the culture extracts against human pathogens are presented as well as the identification of an antimicrobial cyclic dipeptide (Cyclo (LPro-LPhe)) isolated from a strain close to Streptomyces thioluteus. Moreover, the implementation of molecular networks applied to UPLC/MS/MS analysis of actinobacterial cocultures allowed us to explore the diversity of metabolites produced under these conditions. The second chapter presents a methodological study to evaluate the capacity of four DNA extraction methods, in terms of richness and composition of the cuticular bacterial microbiota, in high-throughput sequencing from Atta cephalotes and Pseudomyrmex penetrator. The results of metabarcoding highlight two methods of extraction and reveal inter- and intraspecific differences in the composition of cuticular bacterial communities. Finally, chapter three describes the composition of the cuticular bacterial microbiota of Camponotus femoratus and Crematogaster levior in ant garden and the results reveal the acquisition in the environment of a part of the microbiota. In parallel, metabolomic analyses of ant’s cuticle show, on the contrary, a greater specificity related to the ant species. Future researches focusing on statistical analysis strategies combining metabarcoding and metabolomics data are discussed.
Le microbiote bactérien cuticulaire des fourmis (Hymenoptera : Formicidae) est connu pour avoir un rôle défensif chez ces insectes sociaux, notamment chez les fourmis attines (Formicidae : Attini) grâce l’utilisation de molécules antimicrobiennes produites par des actinobactéries cuticulaires. Dans le cadre de cette thèse, nous avons étudié le microbiote bactérien des fourmis de Guyane en utilisant différentes approches en chimie des produits naturels et en écologie moléculaire. Le premier chapitre décrit l’isolement, l’identification, la culture et l’évaluation biologique de 43 actinobactéries cuticulaires de fourmis de Guyane. Les tests d’antagonismes des souches isolées et l’activité antibiotique des extraits de culture contre des micro-organismes pathogènes humains sont présentés ainsi que l’identification d’un dipeptide cyclique (Cyclo(LPro-LPhe)) antimicrobien qui a été isolé à partir d’une souche proche de Streptomyces thioluteus. Par ailleurs, la mise en œuvre de réseaux moléculaires appliqués à une analyse par UPLC/MS/MS de cocultures d’actinobactéries a permis d’explorer la diversité des métabolites produits dans ces conditions. Le deuxième chapitre présente une étude méthodologique pour comparer quatre méthodes d’extraction d’ADN, en termes de richesse et de composition du microbiote bactérien cuticulaire, par séquençage haut débit à partir des espèces Atta cephalotes et Pseudomyrmex penetrator. Les résultats du métabarcoding ADN mettent en lumière deux méthodes d’extraction et révèlent des différences inter- et intraspécifiques dans la composition des communautés bactériennes cuticulaires. Enfin, le chapitre trois décrit la composition du microbiote bactérien cuticulaire des espèces Camponotus femoratus et Crematogaster levior dans les jardins de fourmis. Les résultats soulignent l’acquisition d’une partie du microbiote dans l’environnement. En parallèle l’analyse métabolomique des cuticules montre à contrario une plus grande spécificité liée à l’espèce de fourmi. Les recherches futures axées sur les stratégies d’analyses statistiques combinant le métabarcoding et la métabolomique sont discutées.
https://tel.archives-ouvertes.fr/tel-01537793

NNT : 2017YANE0003
tel-01537793
https://tel.archives-ouvertes.fr/tel-01537793
https://tel.archives-ouvertes.fr/tel-01537793/document
https://tel.archives-ouvertes.fr/tel-01537793/file/thesecarolinebirer.pdf

Éditeur(s) : HAL CCSD Royal Society of Chemistry
Résumé : Fluorescence is a remarkable property of many natural products in addition to their medicinal and biological values. Herein, we provide a review on these peculiar secondarymetabolites to stimulate prospecting of them as original fluorescent tracers, endowed with unique photophysical properties and with applications in most fields of biology. The compounds are spectrally categorized (i.e. fluorescing from violet to the near infra-red) and further structurally classified within each category. Natural products selected for their high impact in modern fluorescence-based biological studies are highlighted throughout the article. Finally, we discuss aspects of chemical ecology where fluorescent natural products might have key evolutionary roles and thus open new research directions in the field.
ISSN: 0265-0568

hal-01604139
https://hal.archives-ouvertes.fr/hal-01604139
DOI : 10.1039/c6np00111d
PRODINRA : 391732
PUBMED : 28125109

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
A major requirement for malaria elimination is the development of transmission-blocking interventions. In vitro transmission-blocking bioassays currently mostly rely on the use of very few Plasmodium falciparum reference laboratory strains isolated decades ago. To fill a piece of the gap between laboratory experimental models and natural systems, the purpose of this work was to determine if culture-adapted field isolates of P. falciparum are suitable for in vitro transmission-blocking bioassays targeting functional maturity of male gametocytes: exflagellation. Plasmodium falciparum isolates were adapted to in vitro culture before being used for in vitro gametocyte production. Maturation was assessed by microscopic observation of gametocyte morphology over time of culture and the functional viability of male gametocytes was assessed by microscopic counting of exflagellating gametocytes. Suitability for in vitro exflagellation-blocking bioassays was determined using dihydroartemisinin and methylene blue. In vitro gametocyte production was achieved using two isolates from French Guiana and two isolates from Cambodia. Functional maturity of male gametocytes was assessed by exflagellation observations and all four isolates could be used in exflagellation-blocking bioassays with adequate response to methylene blue and dihydroartemisinin. This work shows that in vitro culture-adapted P. falciparum field isolates of different genetic background, from South America and Southeast Asia, can successfully be used for bioassays targeting the male gametocyte to gamete transition, exflagellation.
ISSN: 1475-2875

Droits : http://creativecommons.org/licenses/by/
pasteur-01182753
https://hal-pasteur.archives-ouvertes.fr/pasteur-01182753
https://hal-pasteur.archives-ouvertes.fr/pasteur-01182753/document
https://hal-pasteur.archives-ouvertes.fr/pasteur-01182753/file/LeBas%20et%202015%20version%20publie%20%281%29.pdf
DOI : 10.1186/s12936-015-0752-x