Abstract

Biofilm-associated infections are difficult to manage or treat as biofilms or biofilm-embedded bacteria are difficult to eradicate. Antimicrobial peptides have gained increasing attention as a possible alternative to conventional drugs to combat drug-resistant microorganisms because they inhibit the growth of planktonic bacteria by disrupting the cytoplasmic membrane. The current study investigated the effects of synthetic peptides (PS1-2, PS1-5, and PS1-6) and conventional antibiotics on the growth, biofilm formation, and biofilm reduction of drug-resistant Pseudomonas aeruginosa and Staphylococcus aureus. The effects of PS1-2, PS1-5, and PS1-6 were also tested in vivo using a mouse model. All peptides inhibited planktonic cell growth and biofilm formation in a dose-dependent manner. They also reduced preformed biofilm masses by removing the carbohydrates, extracellular DNA, and lipids that comprised extracellular polymeric substances (EPSs) but did not affect proteins. In vivo, PS1-2 showed the greatest efficacy against preformed biofilms with no cytotoxicity. Our findings indicate that the PS1-2 peptide has potential as a next-generation therapeutic drug to overcome multidrug resistance and to regulate inflammatory response in biofilm-associated infections.

Highlights

  • Biofilm consists of microorganisms embedded in a self-produced matrix of extracellular polymeric substances (EPSs) containing polysaccharides, extracellular DNA, proteins, and lipids [1,2,3].The emergence of multidrug-resistant microorganisms in clinical therapeutics is a global healthcare concern

  • Antimicrobial peptides (AMPs) have gained increasing attention as a possible alternative to conventional drugs to combat drug-resistant microorganisms because they inhibit the growth of planktonic bacteria by disrupting the cytoplasmic membrane and inhibiting intracellular macromolecules

  • These results indicate that AMPs can prevent the proliferation of both drug-resistant and drug-susceptible bacteria owing to their quick and efficient bactericidal mechanisms

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Summary

Introduction

Biofilm consists of microorganisms embedded in a self-produced matrix of extracellular polymeric substances (EPSs) containing polysaccharides, extracellular DNA, proteins, and lipids [1,2,3].The emergence of multidrug-resistant microorganisms in clinical therapeutics is a global healthcare concern. The National Institutes of Health in the USA reported that approximately 80% of chronic. Infectious processes in biofilm are divided into two types, namely device- and non-device-associated infections [5]. Device-associated infections are caused by microbial colonization of medical devices such as urinary catheters, bone joints, heart valves, dental implants, prostheses, contact lenses, and endotracheal tubes [5,6,7,8,9,10]. The occurrence of nosocomial infections through biomaterials or implants is approximately 60–70%; of those, 720,000 cases of central line-associated bloodstream infections occur annually in the USA via dialysis and intensive care units with an associated 12% mortality and a $45,000 increase in treatment cost per episode [11]

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