Global transcriptomic response of the AI-3 isomers 3,5-DPO and 3,6-DPO in Salmonella Typhimurium

Bacterial intercellular signaling mediated by small molecules, also called autoinducers (AIs), enables synchronized behavior in response to environmental conditions, and in many bacterial pathogens, intercellular signaling controls virulence gene expression. However, in the intestinal pathogen Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium), although three signals, named AI-1, AI-2 and AI-3, have been described, their roles in virulence remain elusive. AI-3 is the 3,6- isomer of a previously described Vibrio cholerae signaling molecule; 3,5-dimethylpyrazin-2-ol (3,5-DPO). To elucidate the role of AI-3/DPO in S. Typhimurium, we have mapped the global transcriptomic responses to 3,5- and 3,6-DPO isomers in S. Typhimurium. Our studies showed that DPO affects expression of almost 8% of all genes. Specifically, expression of several genes involved in gut-colonization respond to DPO. Interestingly, most of the affected genes are similarly regulated by 3,5-DPO and 3,6-DPO, respectively, indicating that the two isomers have overlapping roles in S. Typhimurium.