Background: Ciprofloxacin (Cip) is the most commonly used quinolone in clinical practice;
however large-scale use has favored the increase of multiresistant pathogenic microorganisms.
Antimicrobial peptides (AMPs) appear to be a promising alternative in potentiating these conventional
Objective: The aim of this study was to evaluate the effect of the peptide Lys-[Trp6]hy-a1 (lys-a1)
on the antimicrobial and antibiofilm activity of ciprofloxacin against clinically relevant gram-negative
Methods: The antimicrobial effects of Cip and lys-a1 were assessed by determining the minimum
inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). The synergistic
action of Cip and lys-a1 was determined by checkerboard assay. The time-kill curve was constructed
for the Cip/lys-a1 combination against Pseudomonas aeruginosa ATCC 9027. The antibiofilm
activity of this combination was analyzed by crystal violet, colony-forming unit count and
atomic force microscopy (AFM).
Results: The data demonstrated that lys-a1 was able to inhibit planktonic growth of strains of P.
aeruginosa and Klebsiella pneumoniae both at 125 μg/mL. The fractional inhibitory concentration
index (FICi) showed a synergistic effect between Cip and lys-a1 against P. aeruginosa, decreasing
the MICs of the individual antimicrobial agents by 4- and 8-fold, respectively. This effect was also
observed for the death kinetics and antibiofilm activity. Analysis of the early biofilms (6 h) as well
as isolated cells by AFM images evidenced the cell perturbation caused by Cip/lys-a1 treatment.
Conclusion: These data suggest that lys-a1 has biotechnological potential as a therapeutic tool for
the treatment of infections caused by clinically relevant microorganisms, especially P. aeruginosa.