Bacterial Signal Transduction Modules: from Genomics to Biology

M icrobial genome sequencing has had only a modest impact on practical microbiology so far. It has not resulted, as many had hoped, in a bonanza of new antimicrobial drugs. The progress in basic understanding of pathogens has also been slow. For example, genomic sequences of the bacteria causing two most common sexually transmitted diseases, Treponema pallidum (syphilis) and Chlamydia trachomatis (vaginitis), were determined more than seven years ago. All their genes have been identified and key metabolic pathways are known, but we still cannot reliably grow either of these pathogens in a cell-free or defined medium. Since every analyzed genome includes numerous genes with unknown functions, a “complete understanding” of any bacterial cell in the framework of systems biology is as yet a murky possibility. In stark contrast to the relatively slow progress in these areas, microbial signal transduction presents a case where genomic data sets have lead to visible progress. The sheer complexity of signal transduction systems, even in model organisms such as Escherichia coli, Bacillus subtilis, and Saccharomyces cerevisiae, has long hindered their systematic analysis. Studies of specific processes, such as nitrogen regulation, chemotaxis, catabolite repression, and sporulation, provide valuable insights into the mechanisms of sensing and signal transduction. However, there had been no easy way to assemble these diverse regulatory systems into a coherent picture. Comparative genomics has changed that by allowing us to predict all regulatory components in a given organism and to compare their organization in various organisms. It has also revealed how much we still do not know about microbial signal transduction.