Abstract

Bacterial outer membrane vesicles (OMVs) are nanometer-scale, spherical vehicles released by Gram-negative bacteria into their surroundings throughout growth. These OMVs have been demonstrated to play key roles in pathogenesis by delivering certain biomolecules to host cells, including toxins and other virulence factors. In addition, this biomolecular delivery function enables OMVs to facilitate intra-bacterial communication processes, such as quorum sensing and horizontal gene transfer. The unique ability of OMVs to deliver large biomolecules across the complex Gram-negative cell envelope has inspired the use of OMVs as antibiotic delivery vehicles to overcome transport limitations. In this review, we describe the advantages, applications, and biotechnological challenges of using OMVs as antibiotic delivery vehicles, studying both natural and engineered antibiotic applications of OMVs. We argue that OMVs hold great promise as antibiotic delivery vehicles, an urgently needed application to combat the growing threat of antibiotic resistance.

Highlights

  • The treatment of bacterial infections continues to be more difficult due to the growing number of antibiotic-resistant organisms and the slow pace of antibiotic discovery

  • We provide examples demonstrating successful application of these vehicles for therapeutic purposes and discuss the limitations that remain to be addressed to enable the translation of outer membrane vesicles (OMVs) as antibiotic delivery vehicles

  • The primary advantage of using OMVs as antibiotic delivery vehicles is their inherent ability to deliver their cargo across the cell envelope of Gram-negative bacteria

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Summary

INTRODUCTION

The treatment of bacterial infections continues to be more difficult due to the growing number of antibiotic-resistant organisms and the slow pace of antibiotic discovery. The role of OMVs in intracellular communication, both between bacterial cells and the host as well as between bacterial cells, has been established [5, 8] This communication is possible due to the ability of the OMVs to deliver a wide range of biomolecules, OMVs for Antibiotic Delivery. The unique ability of OMVs to deliver molecules across the Gram-negative cell envelope [10, 14, 16,17,18,19] suggests that OMVs have potential as natural antibiotic delivery vehicles to overcome the limitations of antibiotic delivery to these difficult-to-treat bacteria [20,21,22,23]. We provide examples demonstrating successful application of these vehicles for therapeutic purposes and discuss the limitations that remain to be addressed to enable the translation of OMVs as antibiotic delivery vehicles

NATURAL FUNCTIONS OF OMVs
Transport Across the Bacterial Cell Envelope
Delivery of Hydrophobic Molecules
Selective Delivery of OMVs to Specific Bacterial Cells
OMV Stability
NATURAL ANTIBIOTIC PROPERTIES OF OMVs
METHODS
Strategies to Increase Vesicle Yield
Engineering to Decrease LPS Toxicity
Strategies for Drug Loading
Surface Engineering
FUTURE DIRECTIONS
Findings
CONCLUSIONS
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