Hua, D. | bioRxiv Science

bioRxiv2019

Broad-Spectrum Antifungal Activities and Mechanism of Drimane Sesquiterpenoids

Eight drimane sesquiterpenoids including (-)-drimenol and (+)-albicanol were synthesized from (+)-sclareolide and evaluated for their antifungal activities. Three compounds, (-)-drimenol, (+)-albicanol, and (1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyl-decahydronaphthalene-1-carbaldehyde (4) showed strong activity against C. albicans. (-)-Drimenol, the strongest inhibitor of the three, (at concentrations of 8 - 64 g/ml, causing 100% death of fungi), acts not only against C. albicans as a fungicidal manner, but also inhibits other fungi such as Aspergillus, Cryptococcus, Pneumocystis, Blastomyces, Fusarium, Rhizopus, Saksenaea and FLU resistant strains of C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. auris. These observations suggest drimenol is a broad-spectrum antifungal agent. At high concentration (100 g/ml), drimenol caused a rupture of the fungal cell wall/membrane. In a nematode model of C. albicans infection, drimenol rescued the worms from C. albicans-mediated death, indicating drimenol is tolerable and bioactive in a metazoan. Genome-wide fitness profiling assays of both S. cerevisiae (nonessential homozygous and essential heterozygous) and C. albicans (Tn-insertion mutants) collections revealed putative genes and pathways affected by drimenol. Using a C. albicans mutants spot assay, the Crk1 kinase associated gene products, Ret2, Cdc37, and novel putative targets orf19.759, orf19.1672, and orf19.4382 were revealed to be the potential targets of drimenol. Further, computational modeling results suggest possible modification of the structure of drimenol including the A ring for improving antifungal activity.

microbiology↗

bioRxiv2019

Multifaceted diversity traits of crucial microbial groups in biological soil crusts promote soil multifunctionality

AbstractsMicrobial diversity is one of the most important drivers on ecosystem to maintain the simultaneous performance of functions (multifunctionality, MF) under climatic oscillation. However, existing studies typically consider taxonomic richness or Shannon index at the community level in which relations between diversity and functioning are not highly consistent. To disentangle the underlying linkages in real-world ecosystems, we conducted field investigation on biological soil crusts of Tibetan Plateau and evaluated multiple diversity facets (i.e., richness, evenness, and phylogeny-related trait dissimilarity) of carbon- and nitrogen-fixing functional groups (FGs). Seven crucial variables of soil functioning were also identified to calculate MF. We found that the integrated index, invoking multiple diversity components, was a stronger predictor on MF than richness. Moreover, the divergent performance of different diversity facets determined the idiosyncratic diversity effect of each FG on the MF. Namely, richness was the dominant factor for diazotrophs to maximize MF, whereas phylogenetic dissimilarity was the most important one for phototrophs. The heterogeneity among the focal FGs derived from the significant differentiation of the extent of multifunctional redundancy. Collectively, we speculated that the multifaceted diversity pattern depicts the response ability of crucial FGs by which biocrusts stabilize MF under environmental perturbation. Taken together, our results provided a perspective to bridge the gap between taxonomic and trait-based approaches for elucidating the biodiversity-ecosystem functioning relationship, and could ultimately help to boost the practices of dryland management against global change.

ecology↗