United we stand, divided we fall: in-depth proteomic evaluation of the synergistic effect of Mo-CBP₃-PepI and Ciprofloxacin against Staphylococcus aureus biofilms

Staphylococcus aureus forms biofilms, a structure that protects bacterial cells, conferring more resistance to difficult treatment. Synthetic peptides surge as an alternative to overcome the biofilm of multidrug-resistant pathogens. Mo-CBP₃-PepI, when combined with Ciprofloxacin, reduced preformed S. aureus biofilm by 50% at low concentrations (0.2 and 6.2 μg. mL⁻¹, respectively). The goal of this study was to evaluate the proteomic profile of biofilms after treatment with the Mo-CBP₃-PepI combined with ciprofloxacin. Here, proteomic analysis confirmed with more depth previously described mechanisms and revealed changes in the accumulation of proteins related to DNA and protein metabolism, cell wall biosynthesis, redox metabolism, quorum sensing, and biofilm formation. Some proteins related to DNA and protein metabolism were reduced, while other proteins, like redox system proteins, disappeared in Ciprofloxacin+Mo-CBP₃-PepI treatment. Our results indicated a synergistic effect of these two molecules with several mechanisms against S. aureus biofilm and opened new doors for combined treatments with other drugs.