Bacteria adapt to environmental stimuli by adjusting their transcriptomes in a complex manner, the full potential of which has yet to be established for any individual bacterial species. Here, we report the transcriptomes of Bacillus subtilis exposed to a wide range of environmental and nutritional conditions that the organism might encounter in nature. We comprehensively mapped transcription units (TUs) and grouped 2935 promoters into regulons controlled by various RNA polymerase sigma factors, accounting for ~66% of the observed variance in transcriptional activity. This global classification of promoters and detailed description of TUs revealed that a large proportion of the detected antisense RNAs arose from potentially spurious transcription initiation by alternative sigma factors and from imperfect control of transcription termination.

Adaptation of cells to environmental changes requires dynamic interactions between metabolic and regulatory networks, but studies typically address only one or a few layers of regulation. For nutritional shifts between two preferred carbon sources of Bacillus subtilis, we combined statistical and model-based data analyses of dynamic transcript, protein, and metabolite abundances and promoter activities. Adaptation to malate was rapid and primarily controlled posttranscriptionally compared with the slow, mainly transcriptionally controlled adaptation to glucose that entailed nearly half of the known transcription regulation network. Interactions across multiple levels of regulation were involved in adaptive changes that could also be achieved by controlling single genes. Our analysis suggests that global trade-offs and evolutionary constraints provide incentives to favor complex control programs.

The human pathogen Staphylococcus aureus is renowned for the rapid colonization of contaminated wounds, medical implants, and food products. Nevertheless, little is known about the mechanisms that allow S. aureus to colonize the respective wet surfaces. The present studies were therefore aimed at identifying factors used by S. aureus cells to spread over wet surfaces, starting either from planktonic or biofilm-associated states. Through proteomics analyses we pinpoint phenol-soluble modulins (PSMs) as prime facilitators of the spreading process. To dissect the roles of the eight PSMs produced by S. aureus, these peptides were chemically synthesized and tested in spreading assays with different psm mutant strains. The results show that PSM␣3 and PSM␥ are the strongest facilitators of spreading both for planktonic cells and cells in catheter-associated biofilms. Compared to the six other PSMs of S. aureus, PSM␣3 and PSM␥ combine strong surfactant activities with a relatively low overall hydropathicity. Importantly, we show that PSM-mediated motility of S. aureus facilitates the rapid colonization of wet surfaces next to catheters and the colonization of fresh meat. S taphylococcus aureus is an opportunistic human pathogen thatcan cause a wide range of acute and chronic diseases, which range from superficial skin infections to life-threatening endocarditis and sepsis (1, 2). The ability of this Gram-positive bacterium to cause these infections depends on the production of secreted and cell wall-associated virulence factors. Of increasing concern is the ability of S. aureus to acquire resistance against antibiotics, as underscored by the global spread of methicillin-resistant S. aureus (MRSA) lineages.Intriguingly, recent proteomics studies have revealed an enormous diversity in the production of virulence factors by different isolates of S. aureus, and only a few of these seem to be invariantly produced (3-5). Among the most commonly identified staphylococcal virulence factors, especially in the community-associated (CA)-MRSA lineages, are the so-called phenol-soluble modulins (PSMs) (6). These PSMs are short, amphipathic, ␣-helical peptides that have leukocidal activity and biosurfactant properties (7-9). The growth media of S. aureus cultures contain both N-terminally formylated and deformylated PSMs, suggesting that these virulence factors are substrates for the bacterial N-formylmethionine deformylase (9, 10).To date, eight PSMs have been identified in S. aureus. These include the four PSM␣1 to PSM␣4 peptides (22 residues each), the PSM␤1 and PSM␤2 peptides (44 residues each), PSM␥ (25 residues) and the recently reported PSM-mec (22 residues). The PSM␣ peptides are encoded by the psm␣ operon, the PSM␤ peptides by the psm␤ operon, and PSM␥ by the hld gene. Notably, the hld gene is embedded within the regulatory RNAIII molecule that is encoded by the agr locus. The gene for PSM-mec was identified in MRSA strains carrying the staphylococcal cassette chromosome mec (SCCmec) types II or III. The expression of all ps...