Enhancement of Antibiofilm Activity of Ciprofloxacin against Staphylococcus aureus by Administration of Antimicrobial Peptides

Muhammad Yasir*, Debarun Dutta, Mark D. P. Willcox

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Staphylococcus aureus can develop resistance by mutation, transfection or biofilm formation. Resistance was induced in S. aureus by growth in sub-inhibitory concentrations of ciprofloxacin for 30 days. The ability of the antimicrobials to disrupt biofilms was determined using crystal violet and live/dead staining. Effects on the cell membranes of biofilm cells were evaluated by measuring release of dyes and ATP, and nucleic acids. None of the strains developed resistance to AMPs while only S. aureus ATCC 25923 developed resistance (128 times) to ciprofloxacin after 30 passages. Only peptides reduced biofilms of ciprofloxacin-resistant cells. The antibiofilm effect of melimine with ciprofloxacin was more (27%) than with melimine alone at 1X MIC (p < 0.001). Similarly, at 1X MIC the combination of Mel4 and ciprofloxacin produced more (48%) biofilm disruption than Mel4 alone (p < 0.001). Combinations of either of the peptides with ciprofloxacin at 2X MIC released ≥ 66 nM ATP, more than either peptide alone (p ≤ 0.005). At 2X MIC, only melimine in combination with ciprofloxacin released DNA/RNA which was three times more than that released by melimine alone (p = 0.043). These results suggest the potential use of melimine and Mel4 with conventional antibiotics for the treatment of S. aureus biofilms.

Original languageEnglish
Article number1159
Issue number10
Publication statusPublished - 24 Sept 2021

Bibliographical note

© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Funding: This work was supported by the Australian Research Council (ARC) under Grant
DP160101664 and the National Health and Medical Research Council under grant APP1183597. First
author acknowledges the UNSW and HEC Pakistan for provision of tuition fee scholarship and
living allowance respectively.


  • Antibiotic resistance
  • Antimicrobial peptides
  • Biofilms
  • Ciprofloxacin
  • Combined effect
  • Staphylococcus aureus


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