Bacterial extracellular vesicles induced oxidative stress and mitophagy through mTOR pathways in colon cancer cells, HT-29: Implications for bioactivity

Marzoog, Thorria R.; Jabir, Majid S.; Ibraheem, Sumayah Abdulhussien; Jawad, Sabrean Farhan; Hamzah, Sawsan S.; Sulaiman, Ghassan M.; Mohammed, Hamdoon A.; Khan, Riaz A.

doi:10.1016/j.bbamcr.2023.119486

Cited by 7 publications

(4 citation statements)

References 51 publications

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“…On the other hand, we observed that almost all amino acid levels were increased, most predominantly in cells treated with pure vesicles. Several studies have shown that bacterial-derived vesicles are associated with the induction of autophagy and mitophagy in host cells [10,[25][26][27] which might lead to the observed increase of amino acid levels.…”

Section: Resultsmentioning

confidence: 99%

Isolation and Quantification of Bacterial Membrane Vesicles for Quantitative Metabolic Studies Using Mammalian Cell Cultures

Kretschmer,

Müller,

Henke

et al. 2023

Cells

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Bacterial membrane vesicles (BMVs) are produced by most bacteria and participate in various cellular processes, such as intercellular communication, nutrient exchange, and pathogenesis. Notably, these vesicles can contain virulence factors, including toxic proteins, DNA, and RNA. Such factors can contribute to the harmful effects of bacterial pathogens on host cells and tissues. Although the general effects of BMVs on host cellular physiology are well known, the underlying molecular mechanisms are less understood. In this study, we introduce a vesicle quantification method, leveraging the membrane dye FM4-64. We utilize a linear regression model to analyze the fluorescence emitted by stained vesicle membranes to ensure consistent and reproducible vesicle–host interaction studies using cultured cells. This method is particularly valuable for identifying host cellular processes impacted by vesicles and their specific cargo. Moreover, it outcompetes unreliable protein concentration-based methods. We (1) show a linear correlation between the number of vesicles and the fluorescence signal emitted from the FM4-64 dye; (2) introduce the “vesicle load” as a new semi-quantitative unit, facilitating more reproducible vesicle-cell culture interaction experiments; (3) show that a stable vesicle load yields consistent host responses when studying vesicles from Pseudomonas aeruginosa mutants; (4) demonstrate that typical vesicle isolation contaminants, such as flagella, do not significantly skew the metabolic response of lung epithelial cells to P. aeruginosa vesicles; and (5) identify inositol monophosphatase 1 (SuhB) as a pivotal regulator in the vesicle-mediated pathogenesis of P. aeruginosa.

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Section: Resultsmentioning

confidence: 99%

Isolation and Quantification of Bacterial Membrane Vesicles for Quantitative Metabolic Studies Using Mammalian Cell Cultures

Kretschmer,

Müller,

Henke

et al. 2023

Cells

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“…Given that essentially all bacteria produce them, bEVs exhibit wide heterogeneity in terms of dimensions, surface elements, and molecular cargo, making this a versatile platform technology for therapeutic development [ 90 ]. In addition, bEVs have the capability to traverse biological barriers while maintaining stability in the bloodstream [ 91 , 92 ]. They also have the potential to deliver their payload with some selectivity to the TME, either by passive accumulation as biological nanoparticles [ 40 , 93 ], by engineered expression of tumor-targeting ligands [ 93 ], or by incorporation into host cells that home to tumors [ 94 ].…”

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

confidence: 99%

“…For instance, Akkermansia muciniphila bEVs can transfer bacterial acetyltransferase to both colorectal cancer cell lines and mouse cancer models, resulting in increased H3K14 acetylation and heat-shock protein 70 (Hsp70) expression, which indirectly induces immune activation of CD8+ cytotoxic T lymphocytes [ 113 ]. The bEVs produced by E. coli strain A5922 were shown to induce oxidative stress, increase PINK1 expression, and reduce mitochondrial membrane potential in HT-29 colon cancer cells, which led to decreased viability [ 92 ]. In HepG2 hepatic cancer cells, Lactobacillus rhamnosus GG bEVs also resulted in a higher Bax/Bcl-2 ratio with activation of apoptosis and subsequent cell death in vitro [ 114 ].…”

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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“…In addition, one similar study discovered that Fusobacterium modulates autophagy to survive, thus aggravating experimental colitis via the miR-574-5p/CARD3 axis[ 20 ]. The latest findings show that bacterial extracellular vesicles induced mitophagy through mTOR pathways relieve oxidative stress in colonic epithelial cells[ 21 ]. Libertellenone T, a compound isolated from Endolichenic fungus , also induces autophagy to strengthen the epithelial barrier function of the colon[ 22 ].…”

Section: Autophagy and Gi Physical Barrier Functionmentioning

confidence: 99%

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

Chang,

Li,

Liu

et al. 2024

World J Gastroenterol

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Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.

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Bacterial extracellular vesicles induced oxidative stress and mitophagy through mTOR pathways in colon cancer cells, HT-29: Implications for bioactivity

Cited by 7 publications

References 51 publications

Isolation and Quantification of Bacterial Membrane Vesicles for Quantitative Metabolic Studies Using Mammalian Cell Cultures

Isolation and Quantification of Bacterial Membrane Vesicles for Quantitative Metabolic Studies Using Mammalian Cell Cultures

Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

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