 One yeast has been extensively used as a model system for analyzing protein-protein and genetic interactions. In the context of bacterial pathogenesis, the use of yeast-based tools has largely been limited to identifying interactions between pathogen effectors and host targets. In their recent work, Ensminger and colleagues, Urbanoset backslash ZA0-L, used backslash ZA0 the combinatorial power of yeast genetics to systematically screen all known Legionella pneumophila effector proteins for effector- effector interactions. They provide new insights into how bacterial effectors balance host cell perturbation and describe mechanisms used by meta-effectors to directly modulate target effector activity. This article was authored by Alan Hewett.