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Whole-Genome Comparison of Mycobacterium tuberculosis Clinical and Laboratory Strains. R. D. Fleischmann, 2002.Virulence and immunity are poorly understood in Mycobacterium tuberculosis. We sequenced the complete genome of the M . tuberculosis clinical strain CDC1551 and performed a whole-genome comparison with the laboratory strain H37Rv in order to identify polymorphic sequences with potential relevance to disease pathogenesis, immunity, and evolution . We found large-sequence and single-nucleotide polymorphisms in numerous genes . Polymorphic loci included a phospholipase C, a membrane lipoprotein, members of an adenylate cyclase gene family, and members of the PE/PPE gene family, some of which have been implicated in virulence or the host immune response . Several gene families, including the PE/PPE gene family, also had significantly higher synonymous and nonsynonymous substitution frequencies compared to the genome as a whole . We tested a large sample of M . tuberculosis clinical isolates for a subset of the large-sequence and single-nucleotide polymorphisms and found widespread genetic variability at many of these loci . We performed phylogenetic and epidemiological analysis to investigate the evolutionary relationships among isolates and the origins of specific polymorphic loci . A number of these polymorphisms appear to have occurred multiple times as independent events, suggesting that these changes may be under selective pressure . Together, these results demonstrate that polymorphisms among M . tuberculosis strains are more extensive than initially anticipated, and genetic variation may have an important role in disease pathogenesis and immunity . Microarray Analysis of Pseudomonas aeruginosa Quorum-Sensing Regulons: Effects of Growth Phase and Environment. Victoria E. Wagner, 2003.Bacterial communication via quorum sensing (QS) has been reported to be important in the production of virulence factors, antibiotic sensitivity, and biofilm development . Two QS systems, known as the las and rhl systems, have been identified previously in the opportunistic pathogen Pseudomonas aeruginosa . High-density oligonucleotide microarrays for the P . aeruginosa PAO1 genome were used to investigate global gene expression patterns modulated by QS regulons . In the initial experiments we focused on identifying las and/or rhl QS-regulated genes using a QS signal generation-deficient mutant (PAO-JP2) that was cultured with and without added exogenous autoinducers [N-(3-oxododecanoyl) homoserine lactone and N-butyryl homoserine lactone] . Conservatively, 616 genes showed statistically significant differential expression (P  0.05) in response to the exogenous autoinducers and were classified as QS regulated . A total of 244 genes were identified as being QS regulated at the mid-logarithmic phase, and 450 genes were identified as being QS regulated at the early stationary phase . Most of the previously reported QS-promoted genes were confirmed, and a large number of additional QS-promoted genes were identified . Importantly, 222 genes were identified as being QS repressed . Environmental factors, such as medium composition and oxygen availability, eliminated detection of transcripts of many genes that were identified as being QS regulated .
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