Bacteriophage-antibiotic combinational treatment is a promising strategy to counter the surge of non-treatable antimicrobial resistant pathogens, and it has been successfully employed in a few critical cases. However, rational design of phage-antibiotic combinations is hindered by the limited knowledge of their underlying mechanisms. The cellular impact of antibiotics and phages alone is highly complex, and often not well understood. This is even more so for phage-antibiotic combinations, which are largely uncharacterized, and might involve molecular mechanisms beyond the regular drug and phage targeted processes. This project deploys an innovative systems biology approach to uncover the molecular underpinnings of phage-antibiotic interactions, and its interplay with the novel phage defense system CBASS.