Abstract

Microbial antagonism is a fundamental ecological process that shapes community composition and maintains ecosystem balance. However, the molecular signals, such as cross-kingdom interactions between bacteria and fungi in natural environments, remain largely unexplored. Lysobacter enzymogenes is a widespread predatory bacterium that produces the antifungal secondary metabolite heat-stable antifungal factor (HSAF), which enables interactions with diverse fungi. Here, we investigated the interkingdom interactions between L. enzymogenes and the environmental fungus Candida krusei, both of which are widely distributed, to elucidate the bacterial-fungal communication. We found that the antagonistic effect of bacteria-fungi was significant under both contact and non-contact co-culture conditions, indicating the involvement of diffusible metabolites. Given that farnesol is a common quorum-sensing (QS) molecule in Candida, metabolite profiling combined with exogenous addition and biosynthesis inhibition experiments demonstrated that farnesol functions as a cross-kingdom signal regulating HSAF production and bacterial antagonism. Further mechanistic analysis of the intrinsic mechanism revealed that the two-component system (TCS) RcsB/C in L. enzymogenes can sense farnesol and activate the production of HSAF through the MarR family regulators, mediating the antagonistic pathway. In addition, our work identified the key amino acid residues in RcsC of L. enzymogenes responsible for recognizing farnesol. In summary, we report the bacterial TCS involved in farnesol sensing and reveal a novel bacterial-fungal antagonistic mechanism, in which L. enzymogenes “hijacks” a fungal QS molecule to enhance its antifungal capacity, uncovering a previously unrecognized strategy of cross-kingdom communication.