Quantifying the effects of antibiotic treatment on the extracellular polymer network of antimicrobial resistant and sensitive biofilms using multiple particle tracking

Lydia C Powell,Mark Gumbleton,Joana Stokniene,David W Thomas,Katja E Hill,Timothy R Walsh,Qiu E Yang,Muthanna Abdulkarim

doi:10.1038/s41522-020-00172-6

Lydia C Powell, Mark Gumbleton + Show 6 more

Open Access

https://doi.org/10.1038/s41522-020-00172-6

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Abstract

Novel therapeutics designed to target the polymeric matrix of biofilms requires innovative techniques to accurately assess their efficacy. Here, multiple particle tracking (MPT) was developed to characterize the physical and mechanical properties of antimicrobial resistant (AMR) bacterial biofilms and to quantify the effects of antibiotic treatment. Studies employed nanoparticles (NPs) of varying charge and size (40–500 nm) in Pseudomonas aeruginosa PAO1 and methicillin-resistant Staphylococcus aureus (MRSA) biofilms and also in polymyxin B (PMB) treated Escherichia coli biofilms of PMB-sensitive (PMBSens) IR57 and PMB-resistant (PMBR) PN47 strains. NP size-dependent and strain-related differences in the diffusion coefficient values of biofilms were evident between PAO1 and MRSA. Dose-dependent treatment effects induced by PMB in PMBSensE. coli biofilms included increases in diffusion and creep compliance (P < 0.05), not evident in PMB treatment of PMBRE. coli biofilms. Our results highlight the ability of MPT to quantify the diffusion and mechanical effects of antibiotic therapies within the AMR biofilm matrix, offering a valuable tool for the pre-clinical screening of anti-biofilm therapies.

Highlights

The important role of bacterial biofilms in chronic human diseases, such as cystic fibrosis, otitis media, chronic skin wounds and implant- and catheter-associated infections, has been increasingly recognized[1]
Using polymyxin B-sensitive (PMBSens) and resistant (PMBR) E. coli strains, we examined the sensitivity of the multiple particle tracking (MPT) biofilm model to detect variations in the biofilm structure after dose-dependent polymyxin B antibiotic therapy in comparison to traditional confocal microscopy
This study has demonstrated the use of MPT with traceable NPs as a robust, non-invasive, in situ technique to inform our understanding of biofilms and further our insight into the potential effects of antimicrobial and anti-biofilm therapies on the biofilm matrix, and on biofilm-related changes induced with the acquisition of antibiotic resistance

Summary

Introduction

The important role of bacterial biofilms in chronic human diseases, such as cystic fibrosis, otitis media, chronic skin wounds and implant- and catheter-associated infections, has been increasingly recognized[1]. MPT has subsequently been employed to characterize the diffusion properties of NPs within biofilms of a range of bacterial species including P. aeruginosa, E. coli, P. fluorescens and S. aureus and to determine time-dependent changes in the biofilm matrix following adhesion[36,37,39,40].

Results

Conclusion