Abstract

Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species. The co-existence of multiple species of bacteria in biofilms exacerbates therapeutic challenges and can render traditional antibiotics ineffective. Polymeric nanoparticles offer alternative antimicrobial approaches to antibiotics, owing to their tunable physico-chemical properties. Here, we report the efficacy of poly(oxanorborneneimide) (PONI)-based antimicrobial polymeric nanoparticles (PNPs) against multi-species bacterial biofilms. PNPs showed good dual-species biofilm penetration profiles as confirmed by confocal laser scanning microscopy. Broad-spectrum antimicrobial activity was observed, with reduction in both bacterial viability and overall biofilm mass. Further, PNPs displayed minimal fibroblast toxicity and high antimicrobial activity in an in vitro co-culture model comprising fibroblast cells and dual-species biofilms of Escherichia coli and Pseudomonas aeruginosa. This study highlights a potential clinical application of the presented polymeric platform.

Highlights

  • Published: 16 August 2021Biofilm infections are a serious health concern due to their high antibiotic tolerance [1].In the United States alone, approximately 1.7 million hospital-acquired infections are associated with biofilms each year, resulting in ~11 billion USD annual economic burden [2].Biofilms are communities of bacterial cells embedded in a self-secreted extracellular polymeric substance (EPS) matrix

  • A 4-day-old dualdual-species biofilm of DsRed-expressing E. coli and green fluorescent protein (GFP)-expressing MRSA was treated for 1 h with coumarin blue-tagged polymeric nanoparticles (PNPs)

  • Micrographs revealed that PNP penetrated the EPS

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Summary

Introduction

Published: 16 August 2021Biofilm infections are a serious health concern due to their high antibiotic tolerance [1].In the United States alone, approximately 1.7 million hospital-acquired infections are associated with biofilms each year, resulting in ~11 billion USD annual economic burden [2].Biofilms are communities of bacterial cells embedded in a self-secreted extracellular polymeric substance (EPS) matrix. Biofilm infections are a serious health concern due to their high antibiotic tolerance [1]. In the United States alone, approximately 1.7 million hospital-acquired infections are associated with biofilms each year, resulting in ~11 billion USD annual economic burden [2]. Biofilms are communities of bacterial cells embedded in a self-secreted extracellular polymeric substance (EPS) matrix. Scarce nutrient and oxygen supplies in the inner layers of the matrix induce the formation of dormant and drug-tolerant persister cells [1,5,6]. Taking all these challenges together, biofilms pose tougher therapeutic challenges than their planktonic counterparts

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