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Simple Summary  The continuous reduction of approved conventional microbicides, due to health concerns and the development of plant-pathogen resistance, has been urged for the use of safe alternatives in crop protection. Several beneficial bacterial species, termed biological control agents, are currently used in lieu of chemical pesticides. The approach to select such bacterial species and manufacture commercial products has been based on their biocontrol effect under optimal growth conditions, which is far from the real nutrient-limited field conditions of plant niches. It’s important to determine the complex interactions that occur among BCAs, plant host and niche microbiome to fully understand and exploit the potential of biological control agents. Furthermore, it’s crucial to acknowledge the environmental impact of their long-term use.    Abstract  Bacterial biological control agents (BCAs) have been increasingly used against plant diseases. The traditional approach to manufacturing such commercial products was based on the selection of bacterial species able to produce secondary metabolites that inhibit mainly fungal growth in optimal media. Such species are required to be massively produced and sustain long-term self-storage. The endpoint of this pipeline is large-scale field tests in which BCAs are handled as any other pesticide. Despite recent knowledge of the importance of BCA-host-microbiome interactions to trigger plant defenses and allow colonization, holistic approaches to maximize their potential are still in their infancy. There is a gap in scientific knowledge between experiments in controlled conditions for optimal BCA and pathogen growth and the nutrient-limited field conditions in which they face niche microbiota competition. Moreover, BCAs are considered to be safe by competent authorities and the public, with no side effects to the environment; the OneHealth impact of their application is understudied. This review summarizes the state of the art in BCA research and how current knowledge and new biotechnological tools have impacted BCA development and application. Future challenges, such as their combinational use and ability to ameliorate plant stress are also discussed. Addressing such challenges would establish their long-term use as centerfold agricultural pesticides and plant growth promoters.

Shifting Perspectives of Translational Research in Bio-Bactericides: Reviewing the Bacillus amyloliquefaciens Paradigm