Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy

Jariah, Rizka Oktarianti Ainun; Hakim, Mohamad S.

doi:10.1002/rmv.2055

Cited by 24 publications

(23 citation statements)

References 157 publications

(341 reference statements)

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“…Bacteriophages (or simply phages) are viruses that exclusively infect bacteria. Interactions between bacteriophages and human or animal organisms play an important role in phage therapy research [2][3][4]. Potential applications of bacteriophages in medicine, as well as general studies of microbiomes in animals and humans, have induced a need for developing tools that facilitate studies of phage circulation and deposition in tissues and cells.…”

Section: Introductionmentioning

confidence: 99%

Circulation of Fluorescently Labelled Phage in a Murine Model

Kaźmierczak

Majewska

Milczarek

et al. 2021

Viruses

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Interactions between bacteriophages and mammals strongly affect possible applications of bacteriophages. This has created a need for tools that facilitate studies of phage circulation and deposition in tissues. Here, we propose red fluorescent protein (RFP)-labelled E. coli lytic phages as a new tool for the investigation of phage interactions with cells and tissues. The interaction of RFP-labelled phages with living eukaryotic cells (macrophages) was visualized after 20 min of co-incubation. RFP-labeled phages were applied in a murine model of phage circulation in vivo. Phages administered by three different routes (intravenously, orally, rectally) were detected through the course of time. The intravenous route of administration was the most efficient for phage delivery to multiple body compartments: 20 min after administration, virions were detected in lymph nodes, lungs, and liver; 30 min after administration, they were detectable in muscles; and 1 h after administration, phages were detected in spleen and lymph nodes. Oral and rectal administration of RFP-labelled phages allowed for their detection in the gastrointestinal (GI) tract only.

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Section: Introductionmentioning

confidence: 99%

Circulation of Fluorescently Labelled Phage in a Murine Model

Kaźmierczak

Majewska

Milczarek

et al. 2021

Viruses

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“…In all strains except GU01, the pronounced bacteriolysis induced by the phage was followed by a small increase in turbidity and a subsequent further decrease. It is not clear whether this pattern reflects an "evolutionary arms race" between the phage and host bacterium (25), but no substantial regrowth of any of the bacterial strains was apparent for up to 24 h after the onset of culture. Together, these results suggested that ⌽EF24C-P2 might be effective for the treatment of E. faecalis infection regardless of the VAN sensitivity of the bacterium.…”

Section: Resultsmentioning

confidence: 99%

“…(VRE) have been described (5)(6)(7)(8)(9)(10)(11)(12). Infection with E. faecalis was found to account for 16% of postoperative endophthalmitis cases in Japan, 25.4% in South Korea, and 31.1% in Sweden (13)(14)(15). The development of alternatives to antibiotics for the treatment of drug-resistant E. faecalis infection is therefore urgently needed.…”

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confidence: 99%

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis

Kishimoto

Ishida

Fukuda

et al. 2019

Antimicrob Agents Chemother

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Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage ΦEF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis. Phage ΦEF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 × 104 cells) into the vitreous. The number of viable bacteria in the eye increased to >1 × 107 CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of ΦEF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.

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“…For example, Yu and colleagues designed cocktails with ‘guard’ phage that inhibit the evolution of phage resistance because they were previously experimentally evolved to infect likely‐to‐evolve resistant cells (Yu et al ., 2018). However, many researchers have described multiple rounds of phage‐host coevolution suggesting that protection by guard phage may be temporary on an evolutionary time scale, although this has not been tested (Koskella and Brockhurst, 2014; Jariah and Hakim, 2019). Others have used molecular techniques to identify phage binding sites and subsequently design cocktails that use multiple binding sites to increase both the number of mutations required for resistance and the cost of resistance (Filippov et al ., 2011).…”

Section: Discussionmentioning

confidence: 99%

Phage cocktail strategies for the suppression of a pathogen in a cross‐feeding coculture

Fazzino

Anisman

Chacón

et al. 2020

Microbial Biotechnology

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Predicting which combinations (cocktails) of bacteria‐infecting viruses (bacteriophage) will suppress pathogenic bacterial growth is complicated, in part, due to the complex ecological interactions of host bacteria, but important for effective treatment. We found that when hosts cross‐feed (exchange nutrients) with nonhost bacterial species, cocktails that include a bacteriophage infecting the nonhost cross‐feeding partner can be more effective at suppressing pathogenic bacteria than targeting the pathogenic bacterium with multiple bacteriophage species. This is a novel cocktail formulation.

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Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy

Cited by 24 publications

References 157 publications

Circulation of Fluorescently Labelled Phage in a Murine Model

Circulation of Fluorescently Labelled Phage in a Murine Model

Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis

Phage cocktail strategies for the suppression of a pathogen in a cross‐feeding coculture

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