Global Effects of the Cell-to-Cell Signaling Molecules Autoinducer-2, Autoinducer-3, and Epinephrine in a luxS Mutant of Enterohemorrhagic Escherichia coli

Intrakingdom cell-to-cell communication and interkingdom cell-to-cell communication play essential roles in the virulence of enterohemorrhagicEscherichia coli (EHEC). Four signals, autoinducer 2 (AI-2), AI-3, and the human hormones epinephrine and norepinephrine, are important in this communication. The effect of these signaling compounds on the transcriptome of EHEC was examined in this study. We demonstrated that theluxS mutation affects primarily central metabolic genes in both pathogenic and nonpathogenic strains ofE. coli and that addition of exogenous AI-2 does not fully restore the expression profile in aluxS -deficient strain lacking the ability to synthesize AI-2. Addition of AI-3 or epinephrine increased expression of the locus of enterocyte effacement regulon, which is known to play a pivotal role in EHEC virulence. Moreover, when epinephrine was added to the culture medium, the greatest number of gene alterations was observed. These alterations included a greater proportion of alterations in EHEC genes than in MG1655 genes, suggesting that epinephrine may be a global virulence signal. Detailed examination with real-time reverse transcriptase PCR (RT-PCR) confirmed the increases in virulence gene expression with addition of AI-3 and epinephrine. Additional studies with real-time RT-PCR examining the EHEC secreted effectors and putative fimbrial gene expression showed a variable expression profile, indicating that there is differential regulation of the secreted molecules. This study began to examine the global signaling networks in EHEC and revealed expression profiles that are signal and pathogen specific.