Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model

Cafora, Marco; Deflorian, Gianluca; Forti, Francesca; Ferrari, Laura; Binelli, Giorgio; Briani, Federica; Ghisotti, Daniela; Pistocchi, Anna

doi:10.1038/s41598-018-37636-x

Cited by 122 publications

(105 citation statements)

References 59 publications

(56 reference statements)

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“…The presence of a developed innate immune system, genetic tractability, and optical transparency of the embryos make it useful for studying aspects of infectious diseases not accessible in traditional animal models. Recently, some zebrafish models were set up to study bacterial infections such as Enterococcus faecalis and P. aeruginosa for phage therapy application [41,42]. Systemic infection in zebrafish embryos is performed through the injection of bacteria in the circulation followed by phage administration via the same route.…”

Section: Phage Therapy and Antimicrobial Action Using Invertebrate Anmentioning

confidence: 99%

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Animal Models to Translate Phage Therapy to Human Medicine

Brix

Cafora

Aureli

et al. 2020

IJMS

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Phagotherapy, the use of bacteriophages to fight bacterial infections as an alternative to antibiotic treatments, has become of increasing interest in the last years. This is mainly due to the diffusion of multi-drug resistant (MDR) bacterial infections that constitute a serious issue for public health. Phage therapy is gaining favor due to its success in agriculture and veterinary treatments and its extensive utilization for human therapeutic protocols in the Eastern world. In the last decades, some clinical trials and compassionate treatments have also been performed in the Western world, indicating that phage therapy is getting closer to its introduction in standard therapy protocols. However, several questions concerning the use of phages in human therapeutic treatments are still present and need to be addressed. In this review, we illustrate the state of art of phage therapy and examine the role of animal models to translate these treatments to humans.

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Section: Phage Therapy and Antimicrobial Action Using Invertebrate Anmentioning

confidence: 99%

“…Immune response and phage therapy were addressed also by Cafora et al (2019) [42] in a zebrafish model of cystic fibrosis (CF). A P. aeruginosa systemic infection was generated in CF zebrafish embryos and treated effectively by phage administration.…”

Section: Phages and Immune System Interactions Studies Using Animal Mmentioning

confidence: 99%

Animal Models to Translate Phage Therapy to Human Medicine

Brix

Cafora

Aureli

et al. 2020

IJMS

Self Cite

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“…We can find more examples of how bacteriophages are being used for human or animal models, in addition to different bioengineering methods using bacteriophages that are currently being developed. [29][30][31] Bacteriophages Used for Accelerated Therapeutic Antibody Production Against the Virus Despite the fact that bacteriophages' potential to fight bacterial infections has only recently been rediscovered, they were successfully used as tools at the molecular level, leading to Nobel Prize awards. 32 Using a technique called phage display, bacteriophages have the potential to quickly produce recombinant antibodies.…”

Section: Natural Bacteriophages' Potential-a Direct Weapon Against Bamentioning

confidence: 99%

Bacteriophages Could Be a Potential Game Changer in the Trajectory of Coronavirus Disease (COVID-19)

Wojewodzic

2020

PHAGE

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The pandemic of the coronavirus disease (Covid-19) has caused the death of at least 270,000 people as of the 8th of May 2020. This work stresses the potential role of bacteriophages to decrease the mortality rate of patients infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The indirect cause of mortality in Covid-19 is miscommunication between the innate and adaptive immune systems, resulting in a failure to produce effective antibodies against the virus on time. Although further research is urgently needed, secondary bacterial infections in the respiratory system could potentially contribute to the high mortality rate observed among the elderly due to Covid-19. If bacterial growth, together with delayed production of antibodies, is a significant contributing factor to Covid-19's mortality rate, then the additional time needed for the human body's adaptive immune system to produce specific antibodies could be gained by reducing the bacterial growth rate in the respiratory system of a patient. Independently of that, the administration of synthetic antibodies against SARS-CoV-2 viruses could potentially decrease the viral load. The decrease of bacterial growth and the covalent binding of synthetic antibodies to viruses should further diminish the production of inflammatory fluids in the lungs of patients (the indirect cause of death). Although the first goal could potentially be achieved by antibiotics, I argue that other methods may be more effective or could be used together with antibiotics to decrease the growth rate of bacteria, and that respective clinical trials should be launched. Both goals can be achieved by bacteriophages. The bacterial growth rate could potentially be reduced by the aerosol application of natural bacteriophages that prey on the main species of bacteria known to cause respiratory failure and should be harmless to a patient. Independently of that, synthetically changed bacteriophages could be used to quickly manufacture specific antibodies against SARS-CoV-2. This can be done via a Nobel Prize awarded technique called ''phage display.'' If it works, the patient is given extra time to produce their own specific antibodies against the SARS-CoV-2 virus and stop the damage caused by an excessive immunological reaction.

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“…[3] Following on some success in other settings, case reports of patients with CF successfully treated with phage suggest phage therapy is a viable option that deserves further investigation. [4][5][6][7] While many of these efforts have focused on Pseudomonas aeruginosa(P. aeruginosa) due to its high level of antibiotic resistance [4,[8][9][10], there may be broader applications for this approach beyond treatment of P.…”

Section: Introductionmentioning

confidence: 99%

Methods for Extraction and Detection of Bacteriophage DNA from the Sputum of Patients with Cystic Fibrosis

Burgener

Secor

Tracy

et al. 2020

Preprint

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There is increasing interest in the pulmonary microbiome's bacterial and viral communities, particularly in the context of chronic airway infections in cystic fibrosis (CF). However, the isolation of microbial DNA from the sputum from patients with CF is technically challenging and the optimal protocols for the analysis of viral species, including bacteriophage, from clinical samples remains challenging. Here, we evaluate a set of methods developed for processing and analyzing sputum from patients with CF with a particular emphasis on detecting bacteriophage viron-derived nucleic acid. We evaluate the impact of bead-beating, deoxyribonuclease digestion, and heating steps in these protocols focusing on the quantitative assessment of Pseudomonas aeruginosa and Pf bacteriophage in sputum as a proof of concept. Based on these comparative data, we describe an optimized protocol for processing sputum from patients with CF and isolating DNA for PCR or sequencing-based studies. These studies will facilitate future assessments of bacteriophage and bacteria in sputum from patients with CF. Author SummaryPatients with cystic fibrosis (CF) have thickened secretions and develop chronic infections in their airways. While we culture bacterial pathogens from expectorated sputum this method favors detection of certain organisms. There is greater understanding that the microbiome with in the airway of patients with cystic fibrosis is varied and contains more than just the bacteria that we selectively culture. Processing sputum is difficult as it is very thick. There are many different ways to process sputum depending on what aspect of the sputum is to be studied. We have an interest in a specific bacteriophage, or a virus that infects bacteria. We sought to find the best method to take sputum from a CF patient and extract DNA so that we could detect both bacteria and bacteriophage DNA. We compared different methods that included different combinations of heat, mechanical homogenization, chemical lysis and DNA extraction by commercially available kits. We describe the method we found easiest to execute and produced the best yield for detection of both bacteria and bacteriophage. Our purpose of publishing this method in detail is to facilitate further study of viral and bacterial communities in the sputum of patients with CF.

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Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model

Cited by 122 publications

References 59 publications

Animal Models to Translate Phage Therapy to Human Medicine

Animal Models to Translate Phage Therapy to Human Medicine

Bacteriophages Could Be a Potential Game Changer in the Trajectory of Coronavirus Disease (COVID-19)

Methods for Extraction and Detection of Bacteriophage DNA from the Sputum of Patients with Cystic Fibrosis

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