Emerging role of microbiota derived outer membrane vesicles to preventive, therapeutic and diagnostic proposes

Jalalifar, Saba; Khamsi, Hassan Morovati; Hosseini‐Fard, Seyed Reza; Karampoor, Sajad; Bajelan, Bahar; Irajian, Gholamreza; Mirzaei, Rasoul

doi:10.1186/s13027-023-00480-4

Cited by 12 publications

(12 citation statements)

References 212 publications

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“…Furthermore, there is some successful clinical experience with bEVs, exemplified by the MenBVac vaccine for Neisseria meningitidis [ 95 ]. As a result of these characteristics, harnessing the immunostimulatory properties of bEVs along with additional engineering (such as incorporation of chemotherapeutic drugs and tumor-targeting ligands) comprises an area of intense research efforts [ 96 – 98 ].…”

Section: Microbiome Revelations Spur Interest In Bugs-as-drugs For Ca...mentioning

confidence: 99%

Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

Karaman,

Pathak,

Bayik

et al. 2024

PAI

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There are a growing number of studies linking the composition of the human microbiome to disease states and treatment responses, especially in the context of cancer. This has raised significant interest in developing microbes and microbial products as cancer immunotherapeutics that mimic or recapitulate the beneficial effects of host-microbe interactions. Bacterial extracellular vesicles (bEVs) are nano-sized, membrane-bound particles secreted by essentially all bacteria species and contain a diverse bioactive cargo of the producing cell. They have a fundamental role in facilitating interactions among cells of the same species, different microbial species, and even with multicellular host organisms in the context of colonization (microbiome) and infection. The interaction of bEVs with the immune system has been studied extensively in the context of infection and suggests that bEV effects depend largely on the producing species. They thus provide functional diversity, while also being nonreplicative, having inherent cell-targeting qualities, and potentially overcoming natural barriers. These characteristics make them highly appealing for development as cancer immunotherapeutics. Both natively secreted and engineered bEVs are now being investigated for their application as immunotherapeutics, vaccines, drug delivery vehicles, and combinations of the above, with promising early results. This suggests that both the intrinsic immunomodulatory properties of bEVs and their ability to be modified could be harnessed for the development of next-generation microbe-inspired therapies. Nonetheless, there remain major outstanding questions regarding how the observed preclinical effectiveness will translate from murine models to primates, and humans in particular. Moreover, research into the pharmacology, toxicology, and mass manufacturing of this potential novel therapeutic platform is still at early stages. In this review, we highlight the breadth of bEV interactions with host cells, focusing on immunologic effects as the main mechanism of action of bEVs currently in preclinical development. We review the literature on ongoing efforts to develop natively secreted and engineered bEVs from a variety of bacterial species for cancer therapy and finally discuss efforts to overcome outstanding challenges that remain for clinical translation.

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Section: Microbiome Revelations Spur Interest In Bugs-as-drugs For Ca...mentioning

confidence: 99%

Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

Karaman,

Pathak,

Bayik

et al. 2024

PAI

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“…Previously, an OMV-based vaccine has been approved for use for meningococcal disease, and their small size, biological nature, and diverse surface antigens make them attractive targets for the development of other vaccines as well. , Furthermore, recent studies have shown that OMVs can be bioengineered to deliver cytotoxic payloads directly to cancer cells, making them a promising tool for targeted cancer therapy. , Moreover, Kim et al demonstrated that bioengineered OMVs can effectively reduce tumors even in the absence of a cytotoxic payload, indicating their potential as a standalone therapeutic agent, further highlighting the potential of OMVs . In addition OMVs have also shown promise as carriers for antibiotics, enzymes, and use as diagnostic agents. − Nonetheless, owing to the inherent heterogeneity of OMVs, their complete utilization as therapeutics faces limitations, underscoring the need for further research and exploration.…”

Section: Introductionmentioning

confidence: 99%

Multivariate Analysis of Individual Bacterial Outer Membrane Vesicles Using Fluorescence Microscopy

Singh,

Nice,

et al. 2024

Chemical & Biomedical Imaging

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Gram-negative bacteria produce outer membrane vesicles (OMVs) that play a critical role in cell−cell communication and virulence. OMVs have emerged as promising therapeutic agents for various biological applications such as vaccines and targeted drug delivery. However, the full potential of OMVs is currently constrained by inherent heterogeneities, such as size and cargo differences, and traditional ensemble assays are limited in their ability to reveal OMV heterogeneity. To overcome this issue, we devised an innovative approach enabling the identification of various characteristics of individual OMVs. This method, employing fluorescence microscopy, facilitates the detection of variations in size and surface markers. To demonstrate our method, we utilize the oral bacterium Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) which produces OMVs with a bimodal size distribution. As part of its virulence, A. actinomycetemcomitans secretes leukotoxin (LtxA) in two forms: soluble and surface associated with the OMVs. We observed a correlation between the size and toxin presence where larger OMVs were much more likely to possess LtxA compared to the smaller OMVs. In addition, we noted that, among the smallest OMVs (<100 nm diameter), the fractions that are toxin positive range from 0 to 30%, while the largest OMVs (>200 nm diameter) are between 70 and 100% toxin positive.

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“…OMVs can carry various virulence factors, such as toxins, enzymes, and lipopolysaccharides, which can be delivered to other bacteria or host cells [ 14 ]. However, they also have therapeutic potential, as they can be loaded with drugs or vaccines and used for targeted delivery [ 15 ]. Fungi-derived EVs have also been demonstrated to have therapeutic potential for modulating the immune system and delivering drugs [ 16 , 17 ].…”

mentioning

confidence: 99%