Human body temperature cues widespread changes in virulence gene expression in uropathogenic <i>Escherichia coli</i>

As a bacterial pathogen enters a human host, it immediately encounters a temperature upshift to 37°C. Mimicking the early hours of infection, we analyzed the transcriptome and proteome of uropathogenic <i>Escherichia coli</i> CFT073 initially grown at 23°C, then shifted to 37°C for 4 h. Temperature caused a change in mRNA expression for 9% of the genome (1% false discovery rate, ≥2-fold); similar impacts were observed for the proteome with a good concordance amongst the most highly temperature-regulated genes. Comparison to <i>E. coli</i> K-12 MC4100 shows temperature to be a more broadly used regulatory cue in the uropathogen. Multiple operons associated with fimbrial adhesion, biofilm formation, immune evasion, and competitor defense show temperature regulation. Multiple fimbrial adhesins (<i>pap</i>, <i>pap-2</i>, <i>foc</i>) are increased in expression at 37°C, while others (<i>ecp</i>) are favored at 23°C. Decreased motility gene expression at 37°C and 23°C is correlated with the thermoregulation of multiple motility repressors (<i>papX</i>, <i>focX</i>, <i>pdeL,</i> and <i>rpoS</i>). Several biofilm formation and c-di-GMP signaling genes showed preferential expression at 37°C, suggesting human body temperature modulates this process. Growth at 37°C promotes a broad set of immune evasion genes (complement evasion, antimicrobial peptide cleavage, phagocyte killing/iron acquisition, copper export) along with genes associated with competitor bacterial and phage defense. RpoS protein expression and the genes it controls show minimal changes during this time course, indicating bacteria enter the host ready to counter diverse stresses in various niches. Together, our studies demonstrate that temperature cues a suite of genes whose expression benefits host colonization and survival.