8/18/2023 0 Comments Gram negative bacteria membrane2.1 Transport Across the Bacterial Cell Envelope In this section, we describe several specific natural functions of OMVs that provide them with advantages that could be harnessed for the delivery of antibiotics. While much focus has been placed on understanding OMV-mediated virulence factor delivery to host cells to understand the role of OMVs in the host-pathogen interaction, it has become clear that OMVs are also used by bacteria to communicate with neighboring bacterial cells by delivering proteins, genetic material, and quorum sensing molecules. One of the primary functions of OMVs is to transport these molecules to other cells, including both host and bacterial cells. 2 Natural Functions of OMVsĭerived from the outer membrane of Gram-negative bacteria, OMVs contain many similar components, including lipids, proteins, peptidoglycan, and nucleic acids, though not necessarily in the same proportions as in the donor cell ( 14, 24– 27). 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. In this paper, we describe the intrinsic delivery functions of OMVs in relation to their potential use as antibiotic delivery vehicles. In particular, the unique ability of OMVs to deliver molecules across the Gram-negative cell envelope ( 10, 14, 16– 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– 23). This communication is possible due to the ability of the OMVs to deliver a wide range of biomolecules, including proteins, lipids, nucleic acids, peptidoglycan, and small molecules to other cells ( 8– 15). In recent years, 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). These bilayered vesicles are derived from the outer membrane of the Gram-negative bacteria, range in size from 50-250 nm in diameter, and contain many of the same components as the outer membrane of the bacterial cell ( 4– 7) ( Figure 1). OMVs are biological spheres that are naturally produced by many, if not all, bacterial species. Like most other cells, Gram-negative bacteria release membrane vesicles, often referred to as outer membrane vesicles (OMVs) to aid in numerous cellular processes. In order to combat Gram-negative-associated infections, research has focused on developing new types of drugs as well as new delivery strategies to overcome the limitations of currently available drugs. Gram-negative bacteria have been reported to be responsible for more than 30% of nosocomial infections, including 70% of infections acquired in intensive care units (ICUs) in the United States ( 3). A majority of the CDC’s biggest antibiotic resistant threats are Gram-negative bacteria, including carbapenem-resistant Acinetobacter and Enterobacterales, and drug-resistant Neisseria gonorrhoeae ( 1). Gram-negative bacteria, in particular, are extremely difficult to treat with many classes of antibiotics due to their complex, dual-membrane cell envelopes ( 2). Recently, the United States Centers for Disease Control and Prevention (CDC) reported that annually, almost three million people develop antibiotic-resistant infections in the United States, and more than 35,000 die as a result ( 1). 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 argue that OMVs hold great promise as antibiotic delivery vehicles, an urgently needed application to combat the growing threat of antibiotic resistance. 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. 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 addition, this biomolecular delivery function enables OMVs to facilitate intra-bacterial communication processes, such as quorum sensing and horizontal gene transfer. These OMVs have been demonstrated to play key roles in pathogenesis by delivering certain biomolecules to host cells, including toxins and other virulence factors. Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA, United Statesīacterial outer membrane vesicles (OMVs) are nanometer-scale, spherical vehicles released by Gram-negative bacteria into their surroundings throughout growth.
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