Étude de la cytotoxicité d’Aspergillus de la section versicolores sur des lignées cellulaires cutanées et pulmonaires

Recent genotypic studies have shown that Aspergillus versicolor, an ubiquitous mold found in our regions included actually 17 species grouped in the sectionVersicolores. The latter appears to be associated with cutaneous and pulmonary symptoms in some residents of contaminated houses. We studied the cytotoxic potential of 19 strains of this new section, isolated from contaminated homes and clinical respiratory samples. Two cell lines were tested: A549 cells representing lung tissue and HaCaT cells representing skin tissue. Their contact with the spores or extracts of these strains has been studied, at different exposure times and concentrations. The spores did not show a significant impact on cell survival at all concentrations and durations of exposure tested. The extracts had a varied impact on cell survival, depending on different species on the one hand, but also within the same species on the other. In-depth studies of the mechanisms of toxicity and of compounds such as sterigmatocystin, a secondary metabolite synthesized by the mold, would allow this work to be completed, by explaining how these new species are responsible for the symptoms experienced.De récentes études génotypiques ont montré qu’Aspergillus versicolor, moisissure ubiquitaire notamment retrouvée dans nos régions, était composé en réalité de 17 espèces regroupées sous la section Versicolores. Cette dernière semble associée à des symptômes cutanés et pulmonaires chez certains résidents de maisons contaminées. Nous avons étudié le potentiel cytotoxique de 19 souches de cette nouvelle section, isolés dans des habitations contaminées et dans des prélèvements respiratoires cliniques. Deux lignées cellulaires ont été testées : des cellules A549 représentant le tissu pulmonaire et des cellules HaCaT, représentant le tissu cutané. Leur mise en contact avec les spores ou les extraits de ces souches a été étudiée, à différents temps d’exposition et concentrations. Les spores n’ont pas montré d’impact significatif sur la survie cellulaire, à toutes concentrations et durées d’exposition testées. Les extraits ont eu quant à eux un retentissement varié sur la survie cellulaire, en fonction des différentes espèces d’une part, mais également au sein des mêmes espèces d’autre part. Des études approfondies des mécanismes de toxicité et de composés telle la stérigmatocystine, métabolite secondaire synthétisé par le champignon, permettraient de compléter ce travail, en expliquant comment ces nouvelles espèces sont responsables des symptômes ressentis

Cellular Cytotoxicity and Oxidative Potential of Recurrent Molds of the Genus Aspergillus Series Versicolores

International audienceMolds are ubiquitous biological pollutants in bioaerosols. Among these molds, the genus Aspergillus is found in the majority of indoor air samples, and includes several species with pathogenic and toxigenic properties. Aspergillus species in the series Versicolores remain little known despite recurrence in bioaerosols. In order to investigate their toxicity, we studied 22 isolates of clinical and environmental origin, corresponding to seven different species of the series Versicolores. Spore suspensions and ethyl acetate extracts prepared from fungal isolates were subjected to oxidative potential measurement using the dithiothreitol (DTT) test and cell survival measurement. The DTT tests showed that all species of the series Versicolores had an oxidative potential, either by their spores (especially for Aspergillus jensenii) or by the extracts (especially from Aspergillus amoenus). Measurements of cell survival of A549 and HaCaT cell lines showed that only the spore suspension containing 105 spores/mL of Aspergillus jensenii caused a significant decrease in survival after 72 h of exposure. The same tests performed with mixtures of 105 spores/mL showed a potentiation of the cytotoxic effect, with a significant decrease in cell survival for mixtures containing spores of two species (on A549 cells, p = 0.05 and HaCaT cells, p = 0.001) or three different species (on HaCaT cells, p = 0.05). Cell survival assays after 72 h of exposure to the fungal extracts showed that Aspergillus puulaauensis extract was the most cytotoxic (IC50 < 25 µg/mL), while Aspergillus fructus caused no significant decrease in cell survival

6-Polyaminosteroid Squalamine Analogues Display Antibacterial Activity against Resistant Pathogens

International audienceA series of 6-polyaminosteroid analogues of squalamine were synthesized with moderate to good yields and evaluated for their in vitro antimicrobial properties against both susceptible and resistant Gram-positive (vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus) and Gram-negative (carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa) bacterial strains. Minimum inhibitory concentrations against Gram-positive bacteria ranged from 4 to 16 µg/mL for the most effective compounds, 4k and 4n, and showed an additive or synergistic effect with vancomycin or oxacillin. On the other hand, the derivative 4f, which carries a spermine moiety like that of the natural trodusquemine molecule, was found to be the most active derivative against all the resistant Gram-negative bacteria tested, with an MIC value of 16 µg/mL. Our results suggest that 6-polyaminosteroid analogues of squalamine are interesting candidates for Gram-positive bacterial infection treatments, as well as potent adjuvants to fight Gram-negative bacterial resistance