The causative agent of the infection Q fever, Coxiella burnetii, is a Gram-negative intracellular bacterial pathogen. In humans, alveolar macrophages constitute a niche for C. burnetii intracellular replication, which occurs in a lysosome-derived vacuole termed the Coxiella‑containing vacuole (CCV). C. burnetii harbours a Dot/Icm type IV secretion system that is essential for bacterial intracellular replication. This secretion system delivers an arsenal of approximately 150 effector proteins directly from the bacteria into the human host cytosol. Studies over the past decade have offered much insights into bacterial effector functions, primarily with a focus on effectors manipulating specific host proteins. Recently it has become apparent that bacterial effectors can regulate each other once inside the host cell and this may be the primary role of a subset of effectors. A system-wide screen was performed to identify functional relationships between C. burnetii effectors. The nuclear C. burnetii effector A (NceA) was found to confer toxicity in Saccharomyces cerevisiae, and this toxicity was alleviated by co‑expression of two other effectors, named Suppress toxicity of NceA A and B (StnA and StnB). This suggests that StnA and StnB can antagonise the activity of NceA. A yeast two-hybrid screen with a HeLa cell cDNA library identified two putative host binding partners of NceA; tyrosyl-DNA phosphodiesterase 2 (TDP2), a DNA repair enzyme, and stromelysin‑1 PDGF‑responsive element binding protein (SPBP), a transcription cofactor of various autophagy-related proteins. HeLa cells engineered to express NceA demonstrate reduced levels of the autophagy receptor SQSTM1. We hypothesise that NceA alters host transcription, through interactions with TDP2 and SPBP, impacting host cell autophagy. The antagonistic relationship of StnA and StnB with NceA suggests their potential involvement in the host biological cascades targeted by NceA. Interestingly, a stnA C. burnetii mutant displayed a multi-CCV phenotype which also indicates a role for this effector in modulating autophagy. This research aims to progress our understanding of these effectors and their interplay with host autophagy function.