Fang Nan,Huihui Song,Min Sun,Lei Cui,Zeran Bian,Jie Yin,Zipeng Lin,Yan Wang
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.
Proteobacteria primarily utilize acyl-homoserine lactones (AHLs) as quorum-sensing signals for intra-/interspecies communication to control pathogen infections. Enzymatic degradation of AHL represents the major quorum-quenching mechanism that has been developed as a promising approach to prevent bacterial infections. Here we identified a novel quorum-quenching mechanism revealed by an effector of the type IVA secretion system (T4ASS) in bacterial interspecies competition. We found that the soil antifungal bacterium Lysobacter enzymogenes OH11 (OH11) could use T4ASS to deliver the effector protein Le1288 into the cytoplasm of another soil microbiome bacterium Pseudomonas fluorescens 2P24 (2P24). Le1288 did not degrade AHL, whereas its delivery to strain 2P24 significantly impaired AHL production through binding to the AHL synthase PcoI. Therefore, we defined Le1288 as LqqE1 ( L ysobacter q uorum- q uenching e ffector 1 ). Formation of the LqqE1-PcoI complex enabled LqqE1 to block the ability of PcoI to recognize/bind S -adenosy-L-methionine, a substrate required for AHL synthesis. This LqqE1-triggered interspecies quorum-quenching in bacteria seemed to be of key ecological significance, as it conferred strain OH11 a better competitive advantage in killing strain 2P24 via cell-to-cell contact. This novel quorum-quenching also appeared to be adopted by other T4ASS-production bacteria. Our findings suggest a novel quorum-quenching that occurred naturally in bacterial interspecies interactions within the soil microbiome by effector translocation. Finally, we presented two case studies showing the application potential of LqqE1 to block AHL signaling in the human pathogen Pseudomonas aeruginosa and the plant pathogen Ralstonia solanacearum .
危险品化学品经营许可证（带存储）