Animal Models of Phage Therapy

Penziner, Samuel; Schooley, Robert T.; Pride, David T.

doi:10.3389/fmicb.2021.631794

Cited by 21 publications

(18 citation statements)

References 140 publications

(248 reference statements)

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“…Multiple research studies conducted in vivo experiments to study phages' therapeutic effect and safety against a wide range of MDR bacteria. They exhibited significant results for killing the bacteria with minimal side effects [88][89][90]. Moreover, the efficacy of phage therapy against MDR P. aeruginosa in animal models was investigated.…”

Section: Discussionmentioning

confidence: 99%

Bacteriophage as a potential therapy to control antibiotic-resistant Pseudomonas aeruginosa infection through topical application onto a full-thickness wound in a rat model

Rezk

Abdelsattar

Elzoghby

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background Antibiotic-resistant Pseudomonas aeruginosa (P. aeruginosa) is one of the most critical pathogens in wound infections, causing high mortality and morbidity in severe cases. However, bacteriophage therapy is a potential alternative to antibiotics against P. aeruginosa. Therefore, this study aimed to isolate a novel phage targeting P. aeruginosa and examine its efficacy in vitro and in vivo. Results The morphometric and genomic analyses revealed that ZCPA1 belongs to the Siphoviridae family and could infect 58% of the tested antibiotic-resistant P. aeruginosa clinical isolates. The phage ZCPA1 exhibited thermal stability at 37 °C, and then, it decreased gradually at 50 °C and 60 °C. At the same time, it dropped significantly at 70 °C, and the phage was undetectable at 80 °C. Moreover, the phage ZCPA1 exhibited no significant titer reduction at a wide range of pH values (4–10) with maximum activity at pH 7. In addition, it was stable for 45 min under UV light with one log reduction after 1 h. Also, it displayed significant lytic activity and biofilm elimination against P. aeruginosa by inhibiting bacterial growth in vitro in a dose-dependent pattern with a complete reduction of the bacterial growth at a multiplicity of infection (MOI) of 100. In addition, P. aeruginosa-infected wounds treated with phages displayed 100% wound closure with a high quality of regenerated skin compared to the untreated and gentamicin-treated groups due to the complete elimination of bacterial infection. Conclusion The phage ZCPA1 exhibited high lytic activity against MDR P. aeruginosa planktonic and biofilms. In addition, phage ZCPA1 showed complete wound healing in the rat model. Hence, this research demonstrates the potential of phage therapy as a promising alternative in treating MDR P. aeruginosa.

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Section: Discussionmentioning

confidence: 99%

Bacteriophage as a potential therapy to control antibiotic-resistant Pseudomonas aeruginosa infection through topical application onto a full-thickness wound in a rat model

Rezk

Abdelsattar

Elzoghby

et al. 2022

Journal of Genetic Engineering and Biotechnology

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“…To this end, careful optimization of injected dose, injection route, frequency, and immunogenicity will be required for each bacterial type and anatomical site targeted with the phage. These efforts will be facilitated by a large body of literature addressing the delivery, biodistribution, and safety of filamentous phages in animal models ranging from mice to non-human primates [34][35][36][37][38][39][40][41][42] . In this regard, the ability to engineer phage variants capable of crossing vascular barriers (including the blood brain barrier [43][44][45][46] ) could prove especially useful for imaging bacterial targets in hard-toaccess locations such as the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

Borg

Ozbakir

et al. 2022

Preprint

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The ability to noninvasively detect bacteria at any depth inside opaque tissues has important applications ranging from infection diagnostics to tracking therapeutic microbes in their mammalian host. Current examples of probes for detecting bacteria with strain-type specificity are largely based on optical dyes, which cannot be used to examine bacteria in deep tissues due to the physical limitation of light scattering. Here, we describe a new biomolecular probe for visualizing bacteria in a cell-type specific fashion using magnetic resonance imaging (MRI). The probe is based on a peptide that selectively binds manganese and is attached in high numbers to the capsid of filamentous phage. By genetically engineering phage particles to display this peptide, we are able to bring manganese ions to specific bacterial cells targeted by the phage, thereby producing MRI contrast. We show that this approach allows MRI-based detection of targeted E. coli strains while discriminating against non-target bacteria as well as mammalian cells. By engineering the phage coat to display a protein that targets cell surface receptors in V. cholerae, we further show that this approach can be applied to image other bacterial targets with MRI. Finally, as a preliminary example of in vivo applicability, we demonstrate MR imaging of phage-labeled V. cholerae cells implanted subcutaneously in mice. The nanomaterial developed here thus represents a path towards noninvasive detection and tracking of bacteria by combining the programmability of phage architecture with the ability to produce three-dimensional images of biological structures at any arbitrary depth with MRI.

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“…The genetic and physiological similarities between the murine and human species allow to investigate the efficacy of phage treatment developped for human medecine. Animals such as mice may only tolerate the injection of low amounts of liquid, particularly when delivered intravenously or intranasally; phages must thus be concentrated in order to accommodate the required inoculum (Penziner et al, 2021).…”

Section: Murine Modelsmentioning

confidence: 99%

Bacteriophage Therapy for Staphylococcus Aureus Infections: A Review of Animal Models, Treatments, and Clinical Trials

Plumet

Ahmad-Mansour

Dunyach-Rémy

et al. 2022

Front. Cell. Infect. Microbiol.

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Staphylococcus aureus (S. aureus) is a common and virulent human pathogen causing several serious illnesses including skin abscesses, wound infections, endocarditis, osteomyelitis, pneumonia, and toxic shock syndrome. Antibiotics were first introduced in the 1940s, leading to the belief that bacterial illnesses would be eradicated. However, microorganisms, including S. aureus, began to develop antibiotic resistance from the increased use and abuse of antibiotics. Antibiotic resistance is now one of the most serious threats to global public health. Bacteria like methicillin-resistant Staphylococcus aureus (MRSA) remain a major problem despite several efforts to find new antibiotics. New treatment approaches are required, with bacteriophage treatment, a non-antibiotic strategy to treat bacterial infections, showing particular promise. The ability of S. aureus to resist a wide range of antibiotics makes it an ideal candidate for phage therapy studies. Bacteriophages have a relatively restricted range of action, enabling them to target pathogenic bacteria. Their usage, usually in the form of a cocktail of bacteriophages, allows for more focused treatment while also overcoming the emergence of resistance. However, many obstacles remain, particularly in terms of their effects in vivo, necessitating the development of animal models to assess the bacteriophage efficiency. Here, we provide a review of the animal models, the various clinical case treatments, and clinical trials for S. aureus phage therapy.

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Animal Models of Phage Therapy

Cited by 21 publications

References 140 publications

Bacteriophage as a potential therapy to control antibiotic-resistant Pseudomonas aeruginosa infection through topical application onto a full-thickness wound in a rat model

Bacteriophage as a potential therapy to control antibiotic-resistant Pseudomonas aeruginosa infection through topical application onto a full-thickness wound in a rat model

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

Bacteriophage Therapy for Staphylococcus Aureus Infections: A Review of Animal Models, Treatments, and Clinical Trials

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