Abstract
Background: In the intracellular pathogen Brucella spp., the activation of the stringent response, a global regulatorynetwork providing rapid adaptation to growth-affecting stress conditions such as nutrient deficiency, is essential forreplication in the host. A single, bi-functional enzyme Rsh catalyzes synthesis and hydrolysis of the alarmone (p)ppGpp, responsible for differential gene expression under stringent conditions.Results: cDNA microarray analysis allowed characterization of the transcriptional profiles of the B. suis 1330 wildtypeand Δrsh mutant in a minimal medium, partially mimicking the nutrient-poor intramacrophagic environment.A total of 379 genes (11.6% of the genome) were differentially expressed in a rsh-dependent manner, of which 198were up-, and 181 were down-regulated. The pleiotropic character of the response was confirmed, as the genesencoded an important number of transcriptional regulators, cell envelope proteins, stress factors, transport systems,and energy metabolism proteins. Virulence genes such as narG and sodC, respectively encoding respiratory nitratereductase and superoxide dismutase, were under the positive control of (p)ppGpp, as well as expression of thecbb3-type cytochrome c oxidase, essential for chronic murine infection. Methionine was the only amino acid whosebiosynthesis was absolutely dependent on stringent response in B. suis.Conclusions: The study illustrated the complexity of the processes involved in adaptation to nutrient starvation,and contributed to a better understanding of the correlation between stringent response and Brucella virulence.Most interestingly, it clearly indicated (p)ppGpp-dependent cross-talk between at least three stress responsesplaying a central role in Brucella adaptation to the host: nutrient, oxidative, and low-oxygen stress.