Response of <i>Escherichia coli</i> chemotaxis pathway to pyrimidine deoxyribonucleosides

Nucleosides are essential components of all living cells. Bacteria use salvage pathways to import nucleosides from their environment and to utilize them for nucleic acid biosynthesis, but also as alternative sources of carbon, nitrogen and energy. Motile bacteria commonly show chemoattraction towards nutritionally valuable compounds, and in this work, we demonstrate that the chemotaxis pathway of <i>Escherichia coli</i> exhibits specific attractant response to pyrimidine nucleosides. The most sensitive response, in the sub-micromolar range, was observed for pyrimidine deoxyribonucleosides, thymidine (deoxythymidine) and deoxycytidine. In contrast, pyrimidine ribonucleosides elicited weaker and less sensitive response, and no response to pyrimidine nucleobases was observed in the micromolar range of concentrations. Furthermore, no response was observed to tested purine nucleosides or nucleobases. Our subsequent analysis revealed that the pathway response to pyrimidine deoxyribonucleosides is mediated by the minor <i>E. coli</i> chemoreceptor Tap, whereas the response to the ribonucleoside uridine relies on a different mechanism. The observed narrow dynamic range of this response indicates that sensing of deoxyribonucleosides is indirect, likely via an unknown periplasmic binding protein that interacts with Tap.IMPORTANCEChemotactic behavior is highly important for bacterial ecology, enabling motile bacteria to locate environments that are optimal for growth, and it became a paradigm for bacterial environmental sensing and signal transduction. However, even for model organisms, the spectrum of stimuli sensed by the chemotaxis pathway is not fully known, which limits our understanding of the physiological and ecological relevance of the chemotactic behavior. Here, we identified pyrimidine deoxyribonucleosides as a novel and highly specific class of chemoeffector metabolites for <i>Escherichia coli</i>, the most studied chemotaxis model. Our work expands the number of bacterial species that exhibit chemotactic responses to nucleotide derivatives, strengthening the notion that pyrimidines and purines constitute a highly important class of chemoeffectors for many bacteria.