Bacteria produce signal molecules (Acyl-Homoserine Lactones, HSLs) that have been shown to impact not only bacterial behaviour, but also the behaviour of eukaryotic cells. This study examined the impact of HSLs on multiple species of amoebae. Amoebae were grown in the presence and absence of HSLs, with and without putative HSL-receptor antagonists, and population growth rate was examined. Calculated parameters included the Minimum Inhibitory Concentration, Inhibitory Concentration at 50%, Lethal Dose and growth rates, as well as the data providing indications of potential receptors involved in the amoeba-HSL interaction. This study found that five out of 17 amoebae strains tested were susceptible to at least one HSL, N- Dodecanoyl-homoserine lactone; Naegleria gruberi, Vermamoeba vermiformis (two strains), Echinamoeba silvestris and Flamella arnhemensis, with one V. vermiformis strain, and E. silvestris being dually sensitive to N-Decanoyl-homoserine lactone and N-Hexanoyl- homoserine lactone, respectively. There appeared to be no correlation between sensitivity and phylogeny. N-Dodecanoyl-homoserine lactone impacted on amoebic growth rate at lower concentrations, suggesting apoptosis/lack of proliferation was occurring, whilst at high concentrations, N-Dodecanoyl-homoserine lactone was instantly lethal to amoebae, suggesting necrosis. This study also found that N-Dodecanoyl-homoserine lactone executed more of a negative effect on amoeba population growth than N-(3-Oxododecanoyl)-homoserine lactone. It also proposes that a Gs G-Protein Coupled Receptor as a potential HSL-receptor in amoebae. This study therefore supports the hypothesis that HSLs interact via a membrane bound receptor. Gs GPCRs are involved in growth and apoptosis, further supporting the role of HSLs as important interkingdom signalling molecules in therapeutic treatments, including cancer treatments.