Anti-biofilm potency of PepR, a viral-derived peptide, againstdrug-resistant Pseudomonas aeruginosa

Background and Aim : Background: The global crisis of antibiotic resistance increases thedemand for the new promising alternative drugs such as antimicrobial peptides (AMPs).Accordingly, the antibiofilm activity of the PepR peptide against P. aeruginosa isolates wasinvestigated for first time in this study.Methods : Two clinical MDR and carbapenem-resistant (CR) P. aeruginosa isolates, and P.aeruginosa ATCC ۲۷۸۵۳ were investigated. The MIC and MBC of PepR were determined. TheMBIC was determined to evaluate inhibitory activity of PepR on biofilm formation and MBEC todispersal activity on preformed biofilm. The relative expression levels of biofilm-associated genesincluding rhlI, rhlR, lasI, lasR, pelB, pilT, PA۰۷۵۶ and PA۲۰۷۰ were analyzed using qRT-PCR.In vivo evaluation of inhibitory effect of pepR on biofilm formation was performed in the mousemodels of P. aeruginosa biofilm-associated subcataneos catheter infection.Results : MIC and MBC of PepR for both MDR and ATCC ۲۷۸۵۳ P. aeruginosa strains were ۸and ۱۶ μg/mL, respectively, while both MIC and MBC against CR strain were ۴ μg/mL. MBICwas estimated to be ۶۴ μg/ml for all strains. MBEC against MDR and ATCC ۲۷۸۵۳- P. aeruginosastrains was ۱۲۸ μg/ml and against CRPA was ۶۴ μg/ml. The bacterial adhesion was significantlyinhibited at concentrations of ۱/۲× and ۱/۴× MIC in all P. aeruginosa isolates (P < ۰.۰۵).Followingtreatment with PepR at ۱/۲×, ۱/۴×, and ۱/۸× MIC, significant inhibition in biofilm formation wasobserved in all isolates (P < ۰.۰۵). PepR at concentration of ۳۲ μg/mL was able to destroy ۶۹.۷%and ۸۱.۳% of MDR P. aeruginosa isolates and ATCC ۲۷۸۵۳ P. aeruginosa biofilms, respectively(P < ۰.۰۳). The expression levels of all genes in isolates treated with ۱/۲ MIC of PepR were downregulatedby more than four-fold compared to the untreated isolates (P < ۰.۰۵). PepR atconcentrations of ۲×, ۴×, and ۸× MIC significantly reduced the biofilm formation in catheterassociatedinfection model by ۳۳%, ۵۲%, and ۶۷%, respectively (P < ۰.۰۵).Conclusion : Considering relatively strong inhibitory and eradication effect of PepR on the P.aeruginosa biofilms in in vitro and in vivo conditions, the peptide could be considered as apromising candidate for designing an antibiofilm drug.

کلیدواژه ها:

Antimicrobial peptides ، PepR ، biofilm ، Pseudomonas aeruginosa