Harnessing contact-dependent killing for next-generation agricultural biocontrol solutions

Plant diseases present a major challenge to global food security, highlighting the critical need for sustainable biocontrol strategies. While the role of diffusible antimicrobial compounds in mediating pathogen suppression by microbial biocontrol agents has been extensively studied, this review sheds light on contact-dependent killing (CDK)—an underappreciated yet powerful mechanism used by both Gram-negative and Gram-positive bacteria. CDK enables precise elimination of competitor microbes through direct cell-to-cell contact, often involving the delivery of lethal effector molecules during interspecies and interkingdom interactions. We explore the historical background, molecular mechanisms, and biocontrol potential of three well-defined CDK systems: the Type VI (T6SS), Type IV (T4SS), and Type VII (T7SS) Secretion Systems. Case examples demonstrate how plant-beneficial bacteria employ CDK weapons to suppress pathogens and enhance plant growth. As an emerging frontier in biocontrol, we also discuss the promise of CDK in designing synergistic microbial consortia, discovering novel biocontrol agents from native plant-associated microbiomes, and enabling innovative applications such as dual-action biopesticides against insects and pathogens, advanced seed coating technologies, and rational microbiome engineering. By integrating classical microbial competition theory with contemporary agricultural practices, this review highlights CDK as a central mechanism driving next-generation biocontrol strategies that support sustainable agriculture and enhance global food security.