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

Abstract

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.

Keywords:

• Mechanisms of antibiofilm action
• proteomic analysis
• antibiofilm synthetic peptide

Acknowledgments

We are grateful to the CAPES, CNPq and Federal University of Ceará for sponsoring this study.

Author contributions

All authors made substantial contributions. The conception and design of the study and acquisition of data, analysis, and interpretation were performed by Nilton A. S. Neto, Tawanny K. B. Aguiar, Rayara J. P. Costa, Felipe P. Mesquita, Lais L. B. de Oliveira, Maria E. A. de Moraes, Raquel C. Montenegro, Rômulo F. Carneiro, Celso S. Nagano^, Cleverson D. T. Freitas, Pedro F. N. Souza. Methodology was carried out by Nilton A. S. Neto, Tawanny K. B. Aguiar, Rômulo F. Carneiro, Celso S. Nagano, Cleverson D. T. Freitas, and Pedro F. N. Souza. Writing and revising the article was carried out by Nilton A. S. Neto, Felipe P. Mesquita, Lais L. B. de Oliveira, and Pedro F. N. Souza.

All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data supporting this study’s findings are available upon request from the corresponding author.

Additional information

Funding

Pedro F. N. Souza has a grant for senior research from CNPq (process number 305003/2022-4).