Resistance of Aspergillus fumigatus conidia to desiccation and their capacity to reach the alveoli are partly due to the presence of a hydrophobic layer composed of a protein from the hydrophobin family, called RodA, which covers the conidial surface. In A. fumigatus there are seven hydrophobins (RodA–RodG) belonging to class I and III. Most of them have never been studied. We constructed single and multiple hydrophobin-deletion mutants until the generation of a hydrophobin-free mutant. The phenotype, immunogenicity, and virulence of the mutants were studied. RODA is the most expressed hydrophobin in sporulating cultures, whereas RODB is upregulated in biofilm conditions and in vivo Only RodA, however, is responsible for rodlet formation, sporulation, conidial hydrophobicity, resistance to physical insult or anionic dyes, and immunological inertia of the conidia. None of the hydrophobin plays a role in biofilm formation or its hydrophobicity. RodA is the only needed hydrophobin in A. fumigatus, conditioning the structure, permeability, hydrophobicity, and immune-inertia of the cell wall surface in conidia. Moreover, the defect of rodlets on the conidial cell wall surface impacts on the drug sensitivity of the fungus.
Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.
17 June 2019 in Proceedings of the National Academy of Sciences
Polar bear (Ursus maritimus) and brown bear (Ursus arctos) are recently diverged species that inhabit vastly differing habitats. Thus, analysis of the polar bear and brown bear genomes represents a unique opportunity to investigate the evolutionary mechanisms and genetic underpinnings of rapid ecological adaptation in mammals. Copy number (CN) differences in genomic regions between closely related species can underlie adaptive phenotypes and this form of genetic variation has not been explored in the context of polar bear evolution. Here, we analyzed the CN profiles of 17 polar bears, 9 brown bears, and 2 black bears (Ursus americanus). We identified an average of 318 genes per individual that showed evidence of CN variation (CNV). Nearly 200 genes displayed species-specific CN differences between polar bear and brown bear species. Principal component analysis of gene CN provides strong evidence that CNV evolved rapidly in the polar bear lineage and mainly resulted in CN loss. Olfactory receptors composed 47% of CN differentiated genes, with the majority of these genes being at lower CN in the polar bear. Additionally, we found significantly fewer copies of several genes involved in fatty acid metabolism as well as AMY1B, the salivary amylase-encoding gene in the polar bear. These results suggest that natural selection shaped patterns of CNV in response to the transition from an omnivorous to primarily carnivorous diet during polar bear evolution. Our analyses of CNV shed light on the genomic underpinnings of ecological adaptation during polar bear evolution. Significance Copy number variation describes the degree to which contiguous genomic regions differ in their number of copies among individuals. Copy number variable regions can drive ecological adaptation, particularly when they contain genes. Here, we compare differences in gene copy numbers among 17 polar bear and 9 brown bear individuals to evaluate the impact of copy number variation on polar bear evolution. Polar bears and brown bears are ideal species for such an analysis as they are closely related, yet ecologically distinct. Our analysis identified variation in copy number for genes linked to dietary and ecological requirements of the bear species. These results suggest that genic copy number variation has played an important role in polar bear adaptation to the Arctic.
Pulque is a culturally important 4,000-year-old traditional Mexican fermented drink. Pulque is produced by adding fresh aguamiel (agave sap) to mature pulque, resulting in a mixture of microbial communities and chemical compositions. We performed shotgun metagenomic sequencing of five stages of pulque fermentation to characterize organismal and functional diversity. We identified 6 genera (Acinetobacter, Lactobacillus, Lactococcus, Leuconostoc, Saccharomyces and Zymomonas) and 10 species (Acinetobacter boissieri, Acinetobacter nectaris, Lactobacillus sanfranciscensis, Lactococcus lactis, Lactococcus piscium, Lactococcus plantarum, Leuconostoc citreum, Leuconostoc gelidum, Zymomonas mobilis and Saccharomyces cerevisiae) that were present ≥ 1% in at least one stage of pulque fermentation. The abundance of genera and species changed during fermentation and was associated with a decrease in sucrose and increases in ethanol and lactic acid, suggesting that resource competition shapes organismal diversity. We also predicted functional profiles, based on organismal gene content, for each fermentation stage and identified an abundance of genes associated with the biosynthesis of folate, an essential B-vitamin. Additionally, we investigated the evolutionary relationships of S. cerevisiae and Z. mobilis, two of the major microbial species found in pulque. For S. cerevisiae, we used a metagenomics assembly approach to identify S. cerevisiae scaffolds from pulque, and performed phylogenetic analysis of these sequences along with a collection of 158 S. cerevisiae strains. This analysis suggests that S. cerevisiae from pulque is most closely related to Asian strains isolated from sake and bioethanol. Lastly, we isolated and sequenced the whole-genomes of three strains of Z. mobilis from pulque and compared their relationship to seven previously sequenced isolates. Our results suggest pulque strains may represent a distinct lineage of Z. mobilis.