A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the space flight environment has never been accomplished because of significant technological and logistical hurdles. Moreover, the effects of space flight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared with identical ground control cultures. Global microarray and proteomic analyses revealed that 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground-based microgravity culture model. Space flight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during space flight missions and provide novel therapeutic options on Earth.

Genomic sequences and expressed sequence tag data for a diverse group of fungi (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Aspergillus nidulans, Neurospora crassa, and Cryptococcus neoformans) provided the opportunity to accurately characterize conserved intronic elements. An examination of large intron data sets revealed that fungal introns in general are short, that 98% or more of them belong to the canonical splice site (ss) class (5GU. . .AG3), and that they have polypyrimidine tracts predominantly in the region between the 5 ss and the branch point. Information content is high in the 5 ss, branch site, and 3 ss regions of the introns but low in the exon regions adjacent to the introns in the fungi examined. The two yeasts have broader intron length ranges and correspondingly higher intron information content than the other fungi. Generally, as intron length increases in the fungi, so does intron information content. Homologs of U2AF spliceosomal proteins were found in all species except for S. cerevisiae, suggesting a nonconventional role for U2AF in the absence of canonical polypyrimidine tracts in the majority of introns. Our observations imply that splicing in fungi may be different from that in vertebrates and may require additional proteins that interact with polypyrimidine tracts upstream of the branch point. Theoretical protein homologs for Nam8p and TIA-1, two proteins that require U-rich regions upstream of the branch point to function, were found. There appear to be sufficient differences between S. cerevisiae and S. pombe introns and the introns of two filamentous members of the Ascomycota and one member of the Basidiomycota to warrant the development of new model organisms for studying the splicing mechanisms of fungi.Based on studies with a limited number of organisms, fungal genes appear to differ from those of higher eukaryotes in that fungal genes have relatively long exons and short introns (14,37,53). From these data, we hypothesized that fungi as a group would have exon and intron features that are similar as well as different from those of higher eukaryotes. Our approach to testing this hypothesis was to compare the exon and intron characteristics of two well-studied members of the Ascomycota group of fungal organisms, the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe (7,12,20,30,34,68), with the intron and exon characteristics of three additional fungi for which genomic sequences and expressed sequence tag (EST) data are available: two filamentous members of the Ascomycota, Aspergillus nidulans and Neurospora crassa (http://www.broad.mit.edu/annotation/fungi /aspergillus/, http://www.broad.mit.edu/annotation/fungi /neurospora/, and http://www.genome.ou.edu/fungal.html) (19,36,72), and a member of the Basidiomycota, Cryptococcus neoformans (http://www-sequence.stanford.edu/group /C.neoformans/ and http://www.genome.ou.edu/cneo.html). The availability of genomic sequences and EST data for the latter three fungi permitted the establishment...

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Pathogenic bacteria utilise a number of mechanisms to cause disease in human hosts. Bacterial pathogens express a wide range of molecules that bind host cell targets to facilitate a variety of different host responses. The molecular strategies used by bacteria to interact with the host can be unique to specific pathogens or conserved across several different species. A key to fighting bacterial disease is the identification and characterisation of all these different strategies. The availability of complete genome sequences for several bacterial pathogens coupled with bioinformatics will lead to significant advances toward this goal.