The Pseudomonas protegens PBL3 secretome exerts antimicrobial activity against Burkholderia glumae by disrupting cell envelope homeostasis and impairing bacterial replication

The effectiveness of antimicrobials used to manage bacterial infections is increasingly threatened by the emergence of antimicrobial resistance. Many conventional antimicrobials act on a single defined target that pathogens can circumvent through target modification or pathway adaptation. In contrast, antimicrobials that disrupt multiple cellular processes may impose greater fitness costs and reduce the likelihood of resistance development, making their discovery a priority for pharmaceutical and agricultural applications. We previously demonstrated that the environmental bacterium Pseudomonas protegens PBL3 secretes a complex mixture of molecules (secretome) with antimicrobial activity against several plants and human pathogens. However, the mechanism underlying this activity remained unknown. Here, we used the plant pathogen Burkholderia glumae to investigate the mode of action of the P. protegens PBL3 secretome. We showed that the P. protegens PLB3 secretome causes extensive cell envelope damage that results in cell death and interferes with bacterial multiplication. Transcriptomic analysis further revealed broad disruption of processes associated with cell-envelope biogenesis and homeostasis and bacterial replication. Collectively, these findings demonstrate that the P. protegens PBL3 secretome acts as a multi-target antimicrobial that could be harnessed in the development of therapeutics to control bacterial infections of agricultural and medical importance.