The Transcriptional Heat Shock Response of Salmonella Typhimurium Shows Hysteresis and Heated Cells Show Increased Resistance to Heat and Acid Stress

Abstract

We investigated if the transcriptional response of Salmonella Typhimurium to temperature and acid variations was hysteretic, i.e. whether the transcriptional regulation caused by environmental stimuli showed memory and remained after the stimuli ceased. The transcriptional activity of non-replicating stationary phase cells of S. Typhimurium caused by the exposure to 45°C and to pH 5 for 30 min was monitored by microarray hybridizations at the end of the treatment period as well as immediately and 30 minutes after conditions were set back to their initial values, 25°C and pH 7. One hundred and two out of 120 up-regulated genes during the heat shock remained up-regulated 30 minutes after the temperature was set back to 25°C, while only 86 out of 293 down regulated genes remained down regulated 30 minutes after the heat shock ceased. Thus, the majority of the induced genes exhibited hysteresis, i.e., they remained up-regulated after the environmental stress ceased. At 25°C the transcriptional regulation of genes encoding for heat shock proteins was determined by the previous environment. Gene networks constructed with up-regulated genes were significantly more modular than those of down-regulated genes, implying that down-regulation was significantly less synchronized than up-regulation. The hysteretic transcriptional response to heat shock was accompanied by higher resistance to inactivation at 50°C as well as cross-resistance to inactivation at pH 3; however, growth rates and lag times at 43°C and at pH 4.5 were not affected. The exposure to pH 5 only caused up-regulation of 12 genes and this response was neither hysteretic nor accompanied of increased resistance to inactivation conditions. Cellular memory at the transcriptional level may represent a mechanism of adaptation to the environment and a deterministic source of variability in gene regulation.

Salmonella enterica subsp. enterica Serovar Heidelberg Food Isolates Associated with a Salmonellosis Outbreak Have Enhanced Stress Tolerance Capabilities

“…They found that acidification changed the transcriptional levels of only a few genes, while heat stress caused widespread transcriptional changes (49). They also found that 85% of the genes upregulated by heat shock remained upregulated 30 min after the reversal to 25°C and that this was associated with increased tolerance to further heat stress or acidification (49). This agrees with our results, which also found global transcriptional changes after heat shock.…”

“…Several recent studies have investigated the transcriptional response of S. enterica to stress. Pin et al exposed Salmonella Typhimurium strain 4/74 stationary-phase cultures to 45°C or pH 5 for 30 min and compared the microarray data from RNA collected (i) during exposure to these conditions, (ii) immediately after reversal to normal conditions, and (iii) at 30 min postreversal with those for control cultures exposed to 25°C and pH 7 (49). They found that acidification changed the transcriptional levels of only a few genes, while heat stress caused widespread transcriptional changes (49).…”

“…Pin et al exposed Salmonella Typhimurium strain 4/74 stationary-phase cultures to 45°C or pH 5 for 30 min and compared the microarray data from RNA collected (i) during exposure to these conditions, (ii) immediately after reversal to normal conditions, and (iii) at 30 min postreversal with those for control cultures exposed to 25°C and pH 7 (49). They found that acidification changed the transcriptional levels of only a few genes, while heat stress caused widespread transcriptional changes (49). They also found that 85% of the genes upregulated by heat shock remained upregulated 30 min after the reversal to 25°C and that this was associated with increased tolerance to further heat stress or acidification (49).…”

“…For instance, Humphrey et al found that Salmonella Enteritidis isolates that were more tolerant of heat, acid, or hydrogen peroxide also better survived desiccation (62). Others have demonstrated that the preexposure of Salmonella Enteritidis (63) and Typhimurium (49) to sublethal temperatures increased their tolerance to both heat and acid in subsequent exposures, indicating an overlap in stress protection systems. Hamilton et al studied the transcriptome of Salmonella Typhimurium in a nonstatic biofilm system and found that, in addition to upregulation of attachment genes, Salmonella Typhimurium upregulated genes involved in the heat and oxidative stress response (64).…”

Non-essential genes form the hubs of genome scale protein function and environmental gene expression networks in Salmonella entericaserovar Typhimurium

“…While the transcriptional responses of S. Typhimurium during growth and in response to different environmental stress conditions have also been detailed [7-10], a systematic analysis of how the S. Typhimurium responses interact with each other has not been performed.…”