A bacterial-killing type IV secretion system as a hidden antifungal device

Interkingdom competition between bacteria and fungi in nutrient-limited environments drives microbial community dynamics, yet the molecular mechanisms enabling bacterial dominance during bacterial-fungal interaction remain poorly characterized. This study reveals a paradigm-shifting role for bacterial type IV secretion system (T4SS) by demonstrating that a specialized bacterial-killing T4SS (T4SS BK ) in Lysobacter enzymogenes serves as a universal cross-kingdom antifungal weapon. Combining genetic, biochemical, and bioinformatical approaches, we show that T4SS BK mediates direct contact-dependent suppression of phylogenetically diverse fungi—including unicellular yeasts and filamentous species—through delivery of a conserved deoxyribonuclease effector, LtdD. Structural characterization reveals that LtdD homologs are evolutionarily conserved across T4SS BK -harboring bacterial lineages, suggesting widespread ecological deployment of this antifungal strategy. These findings overturn the classical dogma of T4SS BK as an antibacterial apparatus and establish it as a multifunctional microbial combat system capable of trans-kingdom interference. By elucidating a DNA-targeting mechanism of fungal growth inhibition, our work not only redefines the ecological role of T4SS BK in microbial warfare but also provides a molecular blueprint for engineering DNA-based antifungal therapies.