Gene expression profiles in group G streptococci under various stress conditions

Background: Streptococcus dysgalactiae subsp. equisimilis (SDSE), similar to Lancefield group A Streptococcus pyogenes (GAS), causes invasive diseases such as life-threatening streptococcal toxic shock syndrome (STSS). Despite their similar genome sequences, SDSE lacks several important virulence factors of GAS, suggesting that SDSE has specific disease-causing systems. Using microarray analysis, we analyzed SDSE for specific transcriptional regulatory systems involved in stress responses, such as the LytSR/LrgAB system, and their transcriptional profiles under stress conditions. Methods: Transcriptional profiling was performed using microarrays to test the effects of eight antibiotics and five growth conditions. These findings were compared with those obtained during intraperitoneal infection in mice. Results: Genes encoding LrgAB, which modulates the murein hydrolase activity of CidAB and inhibits autolysis in Staphylococcus aureus, were upregulated by exposure to antibacterial agents, phosphate buffered saline (PBS) and stationary phase conditions and during intraperitoneal infection in mice. Starvation and anaerobic conditions stimulated the expression of the streptolysin S operon and polysaccharide lyases in SDSE. Catabolite-responsive elements (cre) were present in the promoter regions of these genes, suggesting that carbon catabolite repression (CCR) is involved in regulating SDSE virulence factors. Comparative genome analysis showed the presence in SDSE of the LytSR/LrgAB system and an additional sigma factor (SDEG_0623), both of which were absent from the GAS genome. Conclusions: These results suggest that the LytSR/LrgAB and CCR play important roles in bacterial resistance to stress microenvironments. Microarray data also indicated that starvation and low oxygen tension partly mimic the microenvironment present during invasive diseases. To assess the transcriptional responses of SDSE under various stress conditions and to predict in vivo microenvironments during invasive diseases, SDSE was transcriptionally profiled using the SDSE-specific microarray. Logarithmically growing SDSE was exposed to the minimum inhibitory concentrations (MIC) of eight antimicrobial agents (penicillin G, erythromycin, levofloxacin, hydrogen peroxide, sodium nitrite, potassium cyanide, carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and mitomycin) for 30 min. Alternatively, SDSE was exposed to five different growth conditions: stationary phase, nutrient starvation conditions (incubation in phosphate buffered saline (PBS), pH 7.4 for 30 min), exposure to 25 mJ UV, partial pressure of atmospheric carbon dioxide with shaking for 30 min, and anaerobic condition.