Phages in a thermoreversible sustained-release formulation targeting E. faecalis in vitro and in vivo

Shlezinger, Mor; Friedman, Michael; Houri‐Haddad, Yael; Hazan, Ronen

doi:10.1371/journal.pone.0219599

Cited by 38 publications

(22 citation statements)

References 44 publications

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“…The formulation was injected into the root canals being further spread intracanal during gelation process and finally sealed. The treatment lasted for 3 weeks and the formulation reduced by 99% enterococci cell counts (Shlezinger et al 2019). Even with few studies applied on this type of infections, further studies could target other relevant pathogens including streptococcal and non-streptococcal bacteria (e.g.…”

Section: Synergymentioning

confidence: 99%

Phage therapy efficacy: a review of the last 10 years of preclinical studies

Melo

Oliveira

Pires

et al. 2020

Critical Reviews in Microbiology

110

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Due to the rise of multidrug-resistant infections in humans, phage therapy is gaining renewed attention in Western medicine. Despite the increasing number of publications focussed on the isolation, characterization and in vitro performance of different phages, there is still a lack of concise pre-clinical information to guide the application of phage therapy in clinical practice. Nevertheless, over the last decade, efforts have been made to conduct more detailed studies of the in vivo efficacy of phages. Here, we review the most relevant in vivo studies performed in the last decade covering phage efficacy in both preclinical and clinical trials. We compare different routes of administration, dosage effect and different animal models of distinct types of infections. Moreover, insights into case studies and results from clinical trials are presented. Challenges and limitations of phage use as evidenced by the current state of research are also discussed in order to improve both the trustworthiness and success of the implementation of phage therapy.

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Section: Synergymentioning

confidence: 99%

Phage therapy efficacy: a review of the last 10 years of preclinical studies

Melo

Oliveira

Pires

et al. 2020

Critical Reviews in Microbiology

110

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“…Generally, reports from recent years indicated a high biodiversity of bacteriophages specific for E. faecalis strains. Such reports can be exemplified by articles describing isolation and characterization of previously unknown phages of different properties [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], genetic modification of known phages and their use in experimental phage therapy (including effects on biofilms) [ 46 , 47 ], assessment of phages in therapy using animal models [ 48 , 49 , 50 , 51 , 52 , 53 ], and cloning of phage genes coding for specific lysins and characterization of the gene products in the light of killing E. faecalis cells [ 54 , 55 , 56 , 57 , 58 , 59 , 60 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Bacteriophage vB_EfaS-271 Infecting Enterococcus faecalis

Topka-Bielecka

Bloch

Nejman-Faleńczyk

et al. 2020

IJMS

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A newly isolated bacteriophage infecting Enterococcus faecalis strains has been characterized, including determination of its molecular features. This phage, named vB_EfaS-271, has been classified as a Siphoviridae member, according to electron microscopy characterization of the virions, composed of a 50 nm-diameter head and a long, flexible, noncontractable tail (219 × 12.5 nm). Analysis of the whole dsDNA genome of this phage showed that it consists of 40,197 bp and functional modules containing genes coding for proteins that are involved in DNA replication (including DNA polymerase/primase), morphogenesis, packaging and cell lysis. Mass spectrometry analysis allowed us to identify several phage-encoded proteins. vB_EfaS-271 reveals a relatively narrow host range, as it is able to infect only a few E. faecalis strains. On the other hand, it is a virulent phage (unable to lysogenize host cells), effectively and quickly destroying cultures of sensitive host bacteria, with a latent period as short as 8 min and burst size of approximately 70 phages per cell at 37 °C. This phage was also able to destroy biofilms formed by E. faecalis. These results contribute to our understanding of the biodiversity of bacteriophages, confirming the high variability among these viruses and indicating specific genetic and functional features of vB_EfaS-271.

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“…This is due to reduced solubility of the PPO segments upon temperature increase (Linse, 1993). Poloxamer 407 has been investigated as a delivery material for bacteriophages, showing gelation of a 30% Poloxamer 407 solution with phage dispersing in 2-3 min at physiological temperatures (Shlezinger et al, 2019). Poloxamer 407 hydrogels released bacteriophages over a 28-day period with daily released phage titers reducing from 10 8 PFU at day 1 to 10 4 PFU at day 28 (Shlezinger et al, 2019).…”

Section: Synthetic Polymersmentioning

confidence: 99%

“…Poloxamer 407 has been investigated as a delivery material for bacteriophages, showing gelation of a 30% Poloxamer 407 solution with phage dispersing in 2-3 min at physiological temperatures (Shlezinger et al, 2019). Poloxamer 407 hydrogels released bacteriophages over a 28-day period with daily released phage titers reducing from 10 8 PFU at day 1 to 10 4 PFU at day 28 (Shlezinger et al, 2019). With an in vitro phage delivery of approximately 1 month, such phage loaded hydrogel systems are a promising development for the treatment of infections where repeated phage administration is not viable or desirable (e.g., orthopedic infections).…”

Section: Synthetic Polymersmentioning

confidence: 99%

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections

et al. 2020

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As viruses with high specificity for their bacterial hosts, bacteriophages (phages) are an attractive means to eradicate bacteria, and their potential has been recognized by a broad range of industries. Against a background of increasing rates of antibiotic resistance in pathogenic bacteria, bacteriophages have received much attention as a possible "last-resort" strategy to treat infections. The use of bacteriophages in human patients is limited by their sensitivity to acidic pH, enzymatic attack and short serum half-life. Loading phage within a biomaterial can shield the incorporated phage against many of these harmful environmental factors, and in addition, provide controlled release for prolonged therapeutic activity. In this review, we assess the different classes of biomaterials (i.e., biopolymers, synthetic polymers, and ceramics) that have been used for phage delivery and describe the processing methodologies that are compatible with phage embedding or encapsulation. We also elaborate on the clinical or preclinical data generated using these materials. While a primary focus is placed on the application of phage-loaded materials for treatment of infection, we also include studies from other translatable fields such as food preservation and animal husbandry. Finally, we summarize trends in the literature and identify current barriers that currently prevent clinical application of phage-loaded biomaterials.

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Phages in a thermoreversible sustained-release formulation targeting E. faecalis in vitro and in vivo

Cited by 38 publications

References 44 publications

Phage therapy efficacy: a review of the last 10 years of preclinical studies

Phage therapy efficacy: a review of the last 10 years of preclinical studies

Characterization of the Bacteriophage vB_EfaS-271 Infecting Enterococcus faecalis

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections

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