Abstract

BackgroundBiofilms are microbial communities surrounded by a self-produced extracellular matrix which protects them from environmental stress. Bacteria within biofilms are 10- to 1000-fold more resistant to antibiotics, making it challenging but imperative to develop new therapeutics that can disperse biofilms and eradicate infection. Gram-negative bacteria produce outer membrane vesicles (OMV) that play critical roles in communication, genetic exchange, cargo delivery, and pathogenesis. We have previously shown that OMVs derived from Burkholderia thailandensis inhibit the growth of drug-sensitive and drug-resistant bacteria and fungi.ResultsHere, we examine the antibiofilm activity of Burkholderia thailandensis OMVs against the oral biofilm-forming pathogen Streptococcus mutans. We demonstrate that OMV treatment reduces biofilm biomass, biofilm integrity, and bacterial cell viability. Both heat-labile and heat-stable components, including 4-hydroxy-3-methyl-2-(2-non-enyl)-quinoline and long-chain rhamnolipid, contribute to the antibiofilm activity of OMVs. When OMVs are co-administered with gentamicin, the efficacy of the antibiotic against S. mutans biofilms is enhanced.ConclusionThese studies indicate that bacterial-derived OMVs are highly effective biological nanoparticles that can inhibit and potentially eradicate biofilms.

Highlights

  • Biofilms are microbial communities surrounded by a self-produced extracellular matrix which protects them from environmental stress

  • outer membrane vesicles (OMV) inhibit S. mutans biofilms and planktonic cultures in a time- and dose-dependent manner We evaluated whether OMVs could disrupt biofilm formation by S. mutans

  • S. mutans was cultured in biofilm medium containing glucose and sucrose (BMGS) on glass slides for 3 days (Fig. 2 A) treated them with OMVs, gentamicin, or PBS

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Summary

Introduction

Biofilms are microbial communities surrounded by a self-produced extracellular matrix which protects them from environmental stress. Gram-negative bacteria naturally and constitutively shed outer membrane vesicles (OMV) from their surface in an active and selective response to extracellular stressors [18, 19]. Several groups, including ours, have reported on the potent antimicrobial activity of OMVs mediated by small molecules, surfactants, and enzymes [28,29,30,31,32,33]. Given their antimicrobial activity and natural occurrence in bacterial biofilms, we hypothesized that OMVs could potentially be useful in treating or disrupting biofilms formed by competitor bacteria. A number of antimicrobial compounds, including peptidoglycan hydrolases, 4-hydroxy3-methyl-2-(2-non-enyl)-quinoline (HMNQ), and longchain rhamnolipid are present in or tightly associate with B. thailandensis OMVs [35]

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