21 research outputs found
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Burkholderia Hep_Hag autotransporter (BuHA) proteins elicit a strong antibody response during experimental glanders but not human melioidosis
Background
The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei.
Results
Using bacteriophage-mediated immunoscreening we identified genes expressed in vivo during experimental equine glanders infection. A family of immunodominant antigens were identified that share protein domain architectures with hemagglutinins and invasins. These have been designated Burkholderia Hep_Hag autotransporter (BuHA) proteins. A total of 110/207 positive clones (53%) of a B. mallei expression library screened with sera from two infected horses belonged to this family. This contrasted with 6/189 positive clones (3%) of a B. pseudomallei expression library screened with serum from 21 patients with culture-proven melioidosis.
Conclusion
Members of the BuHA proteins are found in other Gram-negative bacteria and have been shown to have important roles related to virulence. Compared with other bacterial species, the genomes of both B. mallei and B. pseudomallei contain a relative abundance of this family of proteins. The domain structures of these proteins suggest that they function as multimeric surface proteins that modulate interactions of the cell with the host and environment. Their effect on the cellular immune response to B. mallei and their potential as diagnostics for glanders requires further study
SMURF: Genomic mapping of fungal secondary metabolite clusters
Fungi produce an impressive array of secondary metabolites (SMs) including mycotoxins, antibiotics and pharmaceuticals. The genes responsible for their biosynthesis, export, and transcriptional regulation are often found in contiguous gene clusters. To facilitate annotation of these clusters in sequenced fungal genomes, we developed the web-based software SMURF (www.jcvi.org/smurf/) to systematically predict clustered SM genes based on their genomic context and domain content. We applied SMURF to catalog putative clusters in 27 publicly available fungal genomes. Comparison with genetically characterized clusters from six fungal species showed that SMURF accurately recovered all clusters and detected additional potential clusters. Subsequent comparative analysis revealed the striking biosynthetic capacity and variability of the fungal SM pathways and the correlation between unicellularity and the absence of SMs. Further genetics studies are needed to experimentally confirm these clusters
What can comparative genomics tell us about species concepts in the genus Aspergillus?
Understanding the nature of species” boundaries is a fundamental
question in evolutionary biology. The availability of genomes from several
species of the genus Aspergillus allows us for the first time to
examine the demarcation of fungal species at the whole-genome level. Here, we
examine four case studies, two of which involve intraspecific comparisons,
whereas the other two deal with interspecific genomic comparisons between
closely related species. These four comparisons reveal significant variation
in the nature of species boundaries across Aspergillus. For example,
comparisons between A. fumigatus and Neosartorya fischeri
(the teleomorph of A. fischerianus) and between A. oryzae
and A. flavus suggest that measures of sequence similarity and
species-specific genes are significantly higher for the A. fumigatus
- N. fischeri pair. Importantly, the values obtained from the
comparison between A. oryzae and A. flavus are remarkably
similar to those obtained from an intra-specific comparison of A.
fumigatus strains, giving support to the proposal that A. oryzae
represents a distinct ecotype of A. flavus and not a distinct
species. We argue that genomic data can aid Aspergillus taxonomy by
serving as a source of novel and unprecedented amounts of comparative data, as
a resource for the development of additional diagnostic tools, and finally as
a knowledge database about the biological differences between strains and
species
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Optimizing procedures for a human genome repository
Large numbers of clones will be generated during the Human Genome Project. As each is characterized, subsets will be identified which are useful to the scientific community at large. These subsets are most readily distributed through public repositories. The American Type Culture Collection (ATCC) is experienced in repository operation, but before this project had no history in managing clones and associated information in large batches instead of individually. This project permitted the ATCC to develop several procedures for automating and thus reducing the cost of characterizing, preserving, and maintaining information about clones