Gene modulation during downshift and high temperature stress reduces intracellular replication and virulence of Salmonella enterica serovar Typhimurium: roles of RpoS

Bacterial pathogens adapt to multiple stress conditions; however, the consequences of these responses on infection are not well understood. Here, the adaptive responses of Salmonella enterica serovar Typhimurium (S. typhimurium) to the combination of nutritional deprivation and high temperature (NDHT) stress were investigated. Microarray analysis revealed extensive modulation of expression of genes involved in several metabolic pathways. Interestingly, the expression of a large number of genes involved in chemotaxis, invasion, motility etc are down regulated. Further studies involved S. typhimurium exposed to high temperature (HT) or grown in minimal media, i.e. nutritional downshift (ND), or the combination, i.e. NDHT. The amounts of secretory proteins reduce greatly during NDHT, but not ND or HT, resulting in lower number of colony forming units (CFU) in different organs post oral infection of mice. The expression of the global regulator, RpoS, is downregulated during NDHT. Deletion of rpoS greatly reduces the amounts of secretory proteins and intracellular replication of S. typhimurium during ND but not HT. Extension of these results to RAW macrophage cells demonstrated lower intracellular replication of S. typhimurium at HT. Overall, this study sheds insights on the adaptive responses of S. typhimurium to a combination of stress conditions, resulting in lower infection. Agilent one-color experiment,Organism: Salmonella Typhimurium ,Agilent-Custom GeneExpression 8x15k designed by Genotypic Technology Pvt. Ltd. (AMADID: 017809) , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)