Type VI secretion systems at the interface between bacteria and eukaryotic cells

Bacterial type VI secretion systems (T6SSs) are molecular devices that traverse the bacterial envelope and mediate the translocation of protein effectors directly into prokaryotic or eukaryotic cells, thereby interfering with diverse cellular processes in target organisms. T6SSs involved in interbacterial competition have been widely described and functionally characterized, together with a remarkable arsenal of cognate toxins. In contrast, comparatively less is known about anti-eukaryotic T6SSs. This review summarizes recent advances in the study of T6SSs that target eukaryotic cells, highlighting their roles in virulence, resistance to environmental predators, and microbial competition. We discuss T6SS-mediated interactions with protozoan predators, fungi, animal hosts and plants, emphasizing the expanding repertoire of T6SS effectors that modulate conserved eukaryotic pathways. Together, these findings reveal the ecological and pathogenic relevance of T6SS-driven trans-kingdom interactions.