CADRE: the Central Aspergillus Data REpository 2012.

The Central Aspergillus Data REpository (CADRE; http://www.cadre-genomes.org.uk) is a public resource for genomic data extracted from species of Aspergillus. It provides an array of online tools for searching and visualising features of this significant fungal genus. CADRE arose from a need within the medical community to understand the human pathogen Aspergillus fumigatus. Due to the paucity of Aspergillus genomic resources 10 years ago, the long-term goal of this project was to collate and maintain Aspergillus genomes as they became available. Since our first release in 2004, the resource has expanded to encompass annotated sequence for eight other Aspergilli and provides much needed support to the international Aspergillus research community. Recent developments, however, in sequencing technology are creating a vast amount of genomic data and, as a result, we shortly expect a tidal wave of Aspergillus data. In preparation for this, we have upgraded the database and software suite. This not only enables better management of more complex data sets, but also improves annotation by providing access to genome comparison data and the integration of high-throughput data.

Aspergillus genomes and the Aspergillus cloud.

Aspergillus Genomes is a public resource for viewing annotated genes predicted by various Aspergillus sequencing projects. It has arisen from the union of two significant resources: the Aspergillus/Aspergillosis website and the Central Aspergillus Data REpository (CADRE). The former has primarily served the medical community, providing information about Aspergillus and associated diseases to medics, patients and scientists; the latter has focused on the fungal genomic community, providing a central repository for sequences and annotation extracted from Aspergillus Genomes. By merging these databases, genomes benefit from extensive cross-linking with medical information to create a unique resource, spanning genomics and clinical aspects of the genus. Aspergillus Genomes is accessible from http://www.aspergillus-genomes.org.uk.

Mitochondrial Complex I Is a Global Regulator of Secondary Metabolism, Virulence and Azole Sensitivity in Fungi.

Recent estimates of the global burden of fungal disease suggest that that their incidence has been drastically underestimated and that mortality may rival that of malaria or tuberculosis. Azoles are the principal class of antifungal drug and the only available oral treatment for fungal disease. Recent occurrence and increase in azole resistance is a major concern worldwide. Known azole resistance mechanisms include over-expression of efflux pumps and mutation of the gene encoding the target protein cyp51a, however, for one of the most important fungal pathogens of humans, Aspergillus fumigatus, much of the observed azole resistance does not appear to involve such mechanisms. Here we present evidence that azole resistance in A. fumigatus can arise through mutation of components of mitochondrial complex I. Gene deletions of the 29.9KD subunit of this complex are azole resistant, less virulent and exhibit dysregulation of secondary metabolite gene clusters in a manner analogous to deletion mutants of the secondary metabolism regulator, LaeA. Additionally we observe that a mutation leading to an E180D amino acid change in the 29.9 KD subunit is strongly associated with clinical azole resistant A. fumigatus isolates. Evidence presented in this paper suggests that complex I may play a role in the hypoxic response and that one possible mechanism for cell death during azole treatment is a dysfunctional hypoxic response that may be restored by dysregulation of complex I. Both deletion of the 29.9 KD subunit of complex I and azole treatment alone profoundly change expression of gene clusters involved in secondary metabolism and immunotoxin production raising potential concerns about long term azole therapy.