Antimicrobial and Antibiofilm Activity of Lys-[Trp6]hy-a1 Combined with Ciprofloxacin Against Gram-Negative Bacteria

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Carneiro, Victor Alves ^{[1, 2]} ; de Oliveira, Simone Torres ^[1] ; Silva, Rondinely Lima ^[1] ; Duarte, Humberlania de Sousa ^[1] ; Silva, Maria Laina ^[1] ; Carneiro Matos, Maria Nagila ^[1] ; Bastos Cavalcante, Rafaela Mesquita ^[1] ; Figueira, Ciro Siqueira ^[1] ; Lorenzon, Esteban Nicolas ^[3] ; Cilli, Eduardo Maffud ^[4] ; Silva da Cunha, Rodrigo Maranguape ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ Ceara UFC, Fac Med, Lab Biofilms & Antimicrobial Agents LaBAM, Sobral - Brazil

^[2] Univ Ctr INTA UNINTA, Ctr Bioprospecting & Appl Mol Expt NUBEM, Sobral - Brazil

^[3] Fed Univ Jatai, Med Res Lab, Jatai - Brazil

^[4] Estadual Univ Sao Paulo UNESP, Dept Biochem & Chem Technol, Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROTEIN AND PEPTIDE LETTERS; v. 27, n. 11, p. 1124-1131, 2020.
• Citações Web of Science: 2

Resumo

Background: Ciprofloxacin (Cip) is the most conunonly 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 drugs. Objective: The aim of this study was to evaluate the effect of the peptide Lys-{[}Trp6]hy-a1 (lys-al) on the antimicrobial and antibiofilm activity of ciprofloxacin against clinically relevant gram-negative bacteria. Methods: The antimicrobial effects of Cip and lys-al were assessed by determining the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). The synergistic action of Cip and lys-al was determined by checkerboard assay. The time-kill curve was constructed for the Cip/lys-al combination against Pseudomonas aeruginosa ATCC 9027. The antihiofilm 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 lig/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 hiofllms (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. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs