Updated publication reference for PubMed record(s): 32457714. Daphnia infochemicals can induce defensive responses in microalgae Scenedesmus spp., including colony formation and flocculation. We investigated the phenomenon using a combination of microalgal biology, physiological ecology, and quantitative isobaric tagging (iTRAQ) proteomics. We have discovered that flocculation as a defense response occurs at the early ‘alarm’ phase and requires increased energy resources, with an important role proposed in cysteine synthesis. It appears to be initially stimulated by the production of an extracellular matrix (mainly composed ofby polysaccharides and fatty acids), and later sustained at the ‘acclimation’ stage through Mitogen-activated protein kinase (MAPK) signalling cascades. Defensive strategies leading to colony formation required investment into fatty acids metabolism, to ensure the accurate separation of membranes during cell division. Furthermore, higher energy demands were required at the alarm phase which subsequently decreased at the acclimation stage, thus suggesting a trade-off between colony formation and support of floc form.