How to Tackle Bacteriophages: The Review of Approaches with Mechanistic Insight

Karczewska, Monika; Strzelecki, Patryk; Szalewska-Pałasz, Agnieszka; Nowicki, Dariusz

doi:10.3390/ijms24054447

Cited by 8 publications

(2 citation statements)

References 274 publications

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“…Therefore, although the immune system is ‘familiar’ with phages, it responds to a huge number of these viruses introduced suddenly into the human or animal organism. Because of the huge diversity of bacteriophages 22 – 24 , including various types of their genetic material (dsDNA, ssDNA, ssRNA, or dsRNA), human and animal cells may respond differentially to different phages. For example, RNA genome phages might be recognized by the TLR3 receptor while those bearing double-stranded DNA genomes may be detected through the TLR9 receptor 25 .…”

Section: Introductionmentioning

confidence: 99%

Bacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model

Podlacha,

Gaffke,

Grabowski

et al. 2024

Nat Commun

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One of the hopes for overcoming the antibiotic resistance crisis is the use of bacteriophages to combat bacterial infections, the so-called phage therapy. This therapeutic approach is generally believed to be safe for humans and animals as phages should infect only prokaryotic cells. Nevertheless, recent studies suggested that bacteriophages might be recognized by eukaryotic cells, inducing specific cellular responses. Here we show that in chickens infected with Salmonella enterica and treated with a phage cocktail, bacteriophages are initially recognized by animal cells as viruses, however, the cGAS-STING pathway (one of two major pathways of the innate antiviral response) is blocked at the stage of the IRF3 transcription factor phosphorylation. This inhibition is due to the inability of RNA polymerase III to recognize phage DNA and to produce dsRNA molecules which are necessary to stimulate a large protein complex indispensable for IRF3 phosphorylation, indicating the mechanism of the antiviral response impairment.

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Section: Introductionmentioning

confidence: 99%

Bacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model

Podlacha,

Gaffke,

Grabowski

et al. 2024

Nat Commun

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“…Potential strategies include (1) removal of bacteria by either filtration [8,9] or centrifugation [10,11], and (2) isolation of personnel from procedures of characterization. However, use of filtration has the risk of phage loss via adherence to filters [12,13]. Use of centrifugation is relatively expensive and presents infection hazards.…”

Section: Introductionmentioning

confidence: 99%

Inactivating Host Bacteria for Characterization and Use of Phages

Chambers,

Wright,

Hunter

et al. 2023

Biophysica

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Phage characterization for research and therapy can involve newly isolated phages propagated in pathogenic bacteria. If so, characterization requires safety-managing the bacteria. In the current study, we adapt a common and inexpensive reagent, PrimeStore (Longhorn Vaccines and Diagnostics, San Antonio, TX, USA), to safety-manage bacteria in 20 min by selectively inactivating the bacteria. No bacterial survivors are observed among >109 bacteria per ml for a representative of both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Bacillus thuringiensis). This procedure causes no detected inactivation of podophage T3, myophage T4 and siphophage 0105phi7-2. Margins of safety for PrimeStore concentration exist for bacterial inactivation and phage non-inactivation. Thus, general applicability is expected. Subsequent dialysis is used to block long-term effects on phages. Nonetheless, comparable tests should be performed for each pathogenic bacterial strain/phage. Electron microscopy of thin sections reveals inactivation-altered bacterial cytoplasm and a non-disintegrated bacterial envelope (ghosts). Ghosting of E. coli includes re-arrangement of the cytoplasm and the release of endotoxin. The activity of the released endotoxin is >99% reduced after subsequent dialysis, which also removes PrimeStore components. Ghosting of B. thuringiensis includes apparent phase separation within the cytoplasm. The primary application envisaged is biophysical and other screening of phages for therapy of infectious disease.

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