13Professional phagocytes detect, pursue, engulf, and kill bacteria. While all professional 14 phagocytes use chemotaxis to locate bacteria, little is known about whether they can 15 discriminate among them, responding preferentially to some bacteria over others. Here we 16 examine the chemotaxis of the soil amoeba and professional phagocyte Dictyostelium 17 discoideum in assays where amoebae were presented with a paired choice of different bacteria. 18We observed variation in the extent to which they pursue different types of bacteria and 19 preferential migration towards Gram-negative over Gram-positive bacteria. Response profiles 20 were similar for amoebae isolated from different geographic locations, suggesting that 21 chemotaxis preferences are not strongly influenced by any local variation in the bacterial 22 community. Because cyclic adenosine monophosphate (cAMP) is a known chemoattractant for 23D. discoideum, we tested whether it mediated the preference for Gram-negative bacteria. 24Chemotaxis was diminished in response to a cAMP-deficient strain of Escherichia coli and 25 enhanced in response to an E. coli strain that overproduces cAMP. We conclude that D. 26 discoideum discriminates at a distance among bacteria and that discrimination is mediated in 27 part by sensing of cAMP. Preferential sensing and response to different bacteria may help to 28 explain why some amoeba-bacterial associations are more prevalent in nature than others. 29 30 31 32