The Enemy of My Enemy: New Insights Regarding Bacteriophage–Mammalian Cell Interactions

Bodner, Katie; Melkonian, Arin L.; Covert, Markus W.

doi:10.1016/j.tim.2020.10.014

Cited by 38 publications

(34 citation statements)

References 90 publications

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“…Viruses 2021, 13, 1754 2 of 10 Bacteriophages can utilize mammalian viruses' route for their entry into the cells as they have been found inside endosomes, lysosomes, Golgi, cytoplasm, and the nucleus of mammalian cells [16,17] and to kill intracellular bacteria [18]. Hence, the involvement of bacteriophages in-activation of Toll-like receptors and alteration of immune cell response is evident [19,20].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism by which phages can enter mammalian cells includes phage uptake through phagocytosis [ 16 ], but it seems to differ for different types of phages [ 17 ]. The T4 phage is reported to transcytose into different organs through their epithelial cell barriers [ 24 ], whereas M13 phages can enter both epithelial and endothelial cells through different types of endocytosis or macropinocytosis [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate Androgen Receptor Expression in LNCaP Prostate Cell Line

Sanmukh

Santos

Barquilha

et al. 2021

Viruses

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Wild-type or engineered bacteriophages have been reported as therapeutic agents in the treatment of several types of diseases, including cancer. They might be used either as naked phages or as carriers of antitumor molecules. Here, we evaluate the role of bacteriophages M13 and T4 in modulating the expression of genes related to cell adhesion, growth, and survival in the androgen-responsive LNCaP prostatic adenocarcinoma-derived epithelial cell line. LNCaP cells were exposed to either bacteriophage M13 or T4 at a concentration of 1 × 105 pfu/mL, 1 × 106 pfu/mL, and 1 × 107 pfu/mL for 24, 48, and 72 h. After exposure, cells were processed for general morphology, cell viability assay, and gene expression analyses. Neither M13 nor T4 exposure altered cellular morphology, but both decreased the MTT reduction capacity of LNCaP cells at different times of treatment. In addition, genes AKT, ITGA5, ITGB1, ITGB3, ITGB5, MAPK3, and PI3K were significantly up-regulated, whilst the genes AR, HSPB1, ITGAV, and PGC1A were down-regulated. Our results show that bacteriophage M13 and T4 interact with LNCaP cells and effectively promote gene expression changes related to anchorage-dependent survival and androgen signaling. In conclusion, phage therapy may increase the response of PCa treatment with PI3K/AKT pathway inhibitors.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate Androgen Receptor Expression in LNCaP Prostate Cell Line

Sanmukh

Santos

Barquilha

et al. 2021

Viruses

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“…For horizontal transfer, the intracellular phages may be acquired by animals by uptake through the gills and guts [37], as was found in mussels, or through water flow systems, as in sponges [38]. The absorbed phages can enter animal cells, for example, through transcytosis, macropinocytosis, phagocytosis, active bacterial infection, or activation of a bacterial carrier [39]. Because symbiotic environments can select specific symbionts in horizontal transfer [36], intracellular viromes can be conserved across animal hosts, which is likely to be the reason why the snail phages are closely related to phages that infect animal-associated bacteria (Fig.…”

Section: Discussionmentioning

confidence: 99%

Arms race in a cell: genomic, transcriptomic, and proteomic insights into intracellular phage–bacteria interplay in deep-sea snail holobionts

et al. 2021

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Background Deep-sea animals in hydrothermal vents often form endosymbioses with chemosynthetic bacteria. Endosymbionts serve essential biochemical and ecological functions, but the prokaryotic viruses (phages) that determine their fate are unknown. Results We conducted metagenomic analysis of a deep-sea vent snail. We assembled four genome bins for Caudovirales phages that had developed dual endosymbiosis with sulphur-oxidising bacteria (SOB) and methane-oxidising bacteria (MOB). Clustered regularly interspaced short palindromic repeat (CRISPR) spacer mapping, genome comparison, and transcriptomic profiling revealed that phages Bin1, Bin2, and Bin4 infected SOB and MOB. The observation of prophages in the snail endosymbionts and expression of the phage integrase gene suggested the presence of lysogenic infection, and the expression of phage structural protein and lysozyme genes indicated active lytic infection. Furthermore, SOB and MOB appear to employ adaptive CRISPR–Cas systems to target phage DNA. Additional expressed defence systems, such as innate restriction–modification systems and dormancy-inducing toxin–antitoxin systems, may co-function and form multiple lines for anti-viral defence. To counter host defence, phages Bin1, Bin2, and Bin3 appear to have evolved anti-restriction mechanisms and expressed methyltransferase genes that potentially counterbalance host restriction activity. In addition, the high-level expression of the auxiliary metabolic genes narGH, which encode nitrate reductase subunits, may promote ATP production, thereby benefiting phage DNA packaging for replication. Conclusions This study provides new insights into phage–bacteria interplay in intracellular environments of a deep-sea vent snail.

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“…Recent works discuss possible mechanisms of phage uptake into mammalian cells (Bodner al. 2020;Goswami et al 2021).…”

Section: Bacteriophage Penetration Of Eukaryotic Cellsmentioning

confidence: 99%

Applications of bacteriophages against intracellular bacteria

Śliwka

Ochocka

Skaradzińska

2021

Critical Reviews in Microbiology

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Infectious diseases pose a significant threat to both human and animal populations. Intracellular bacteria are a group of pathogens that invade and survive within the interior of eukaryotic cells, which in turn protect them from antibacterial drugs and the host immune system. Limited penetration of antibacterials into host cells results in insufficient bacterial clearance and treatment failure. Bacteriophages have, over the decades, been proved to play an important role in combating bacterial infections (phage therapy), making them an important alternative to classical antibiotic strategies today. Phages have been found to be effective at killing various species of extracellular bacteria, but little is still known about how phages control intracellular infections. With advances in phage genomics and mechanisms of delivery and cell uptake, the development of phagebased antibacterial strategies to address the treatment of intracellular bacteria has general potential. In this review, we present the current state of knowledge regarding the application of bacteriophages against intracellular bacteria. We cover phage deployment against the most common intracellular pathogens with special attention to therapeutic and preventive strategies.

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The Enemy of My Enemy: New Insights Regarding Bacteriophage–Mammalian Cell Interactions

Cited by 38 publications

References 90 publications

Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate Androgen Receptor Expression in LNCaP Prostate Cell Line

Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate Androgen Receptor Expression in LNCaP Prostate Cell Line

Arms race in a cell: genomic, transcriptomic, and proteomic insights into intracellular phage–bacteria interplay in deep-sea snail holobionts

Applications of bacteriophages against intracellular bacteria

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