Epinecidin-1 Has Immunomodulatory Effects, Facilitating Its Therapeutic Use in a Mouse Model of Pseudomonas aeruginosa Sepsis

Abstract

e Antimicrobial peptides (AMPs) are garnering attention as possible alternatives to antibiotics. Here, we describe the antimicrobial properties of epinecidin-1 against a multidrug-resistant clinical isolate of P. aeruginosa (P. aeruginosa R) and a P. aeruginosa strain from ATCC (P. aeruginosa ATCC 19660) in vivo. The MICs of epinecidin-1 against P. aeruginosa R and P. aeruginosa ATCC 19660 were determined and compared with those of imipenem. Epinecidin-1 was found to be highly effective at combating peritonitis infection caused by P. aeruginosa R or P. aeruginosa ATCC 19660 in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that epinecidin-1 enhances the rate of survival of mice infected with the bacterial pathogen P. aeruginosa through both antimicrobial and immunomodulatory effects.

The SmeYZ Efflux Pump of Stenotrophomonas maltophilia Contributes to Drug Resistance, Virulence-Related Characteristics, and Virulence in Mice

“…Virulence was evaluated by mortality in a murine model of septicemia generated by intraperitoneal injection (33). Groups of 8-week-old male C57BL/6 mice were infected intraperitoneally with the wild-type KJ and mutant KJ⌬YZ (10 9 CFU; 5 mice for each dose).…”

Efficacy of the antimicrobial peptide TP4 against Helicobacter pylori infection: in vitro membrane perturbation via micellization and in vivo suppression of host immune responses in a mouse model

“…TP4 is of the Tilapia Piscidin class of AMPs, with potential activity against many pathogenic and clinically challenging species, but reportedly not against Helicobacter species [ 29 ]. Much like the AMP Epinecidin-1, TP4 rapidly kills both Gram negative and positive bacteria [ 56 ]. Here, we provide both in vitro and in vivo experimental confirmation that TP4 possesses potent antimicrobial activity against H. pylori , and report that TP4 permeates the bacterial membrane and balances the host immune response in a mouse model of H. pylori infection.…”

Host-defense peptides of the skin with therapeutic potential: From hagfish to human

“…Co-injection of mice with epinecidin-1 and Pseudomonas aeruginosa results in increased circulating concentrations of IgG1, indicating that the peptide may enhance the Th2 cell adaptive immune response to infection, as well as producing a dose-dependent elevation in the plasma concentrations of the antiinflammatory cytokine IL-10 [68]. Further studies demonstrated that epinecidin-1 is effective at combating peritonitis infection caused by a multi-drug resistant strain of P. aeruginosa in a mouse model of sepsis, without any adverse behavioral effects or liver or kidney toxicity [85]. Similarly, topical treatment of mice with a trauma-mediated methicillin-resistant S. aureus (MRSA) skin infection with epinecidin-1 increases survival and decreases serum concentrations of the pro-inflammatory cytokines TNF-␣, and IL-6, as well as regulating the recruitment of monocytes and clearance of lymphocytes around the wound region during healing [59].…”