Blood kinetics of four intraperitoneally administered therapeutic candidate bacteriophages in healthy and neutropenic mice

Uchiyama, Jumpei; Maeda, Yoshihiro; Takemura, Iyo; Chess-Williams, Russ; Wakiguchi, Hiroshi; Matsuzaki, Shigenobu

doi:10.1111/j.1348-0421.2009.00125.x

Cited by 28 publications

(21 citation statements)

References 12 publications

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“…Using BlastP searches we identified predicted proteins with a sequence identity between 43 to 99% to Pseudomonas phage KPP10 proteins [13] (Additional file 1, Table S1). Although phage KPP10 shares a similar morphology to JG004 with a head size of 72 nm and a tail length of 116 nm, genome alignments revealed that only 8% of the KPP10 genome shares similarities between 66% and 95% to JG004.…”

Section: Resultsmentioning

confidence: 99%

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Sequencing and Characterization of Pseudomonas aeruginosa phage JG004

et al. 2011

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BackgroundPhages could be an important alternative to antibiotics, especially for treatment of multiresistant bacteria as e.g. Pseudomonas aeruginosa. For an effective use of bacteriophages as antimicrobial agents, it is important to understand phage biology but also genes of the bacterial host essential for phage infection.ResultsWe isolated and characterized a lytic Pseudomonas aeruginosa phage, named JG004, and sequenced its genome. Phage JG004 is a lipopolysaccharide specific broad-host-range phage of the Myoviridae phage family. The genome of phage JG004 encodes twelve tRNAs and is highly related to the PAK-P1 phage genome. To investigate phage biology and phage-host interactions, we used transposon mutagenesis of the P. aeruginosa host and identified P. aeruginosa genes, which are essential for phage infection. Analysis of the respective P. aeruginosa mutants revealed several characteristics, such as host receptor and possible spermidine-dependance of phage JG004.ConclusionsWhole genome sequencing of phage JG004 in combination with identification of P. aeruginosa host genes essential for infection, allowed insights into JG004 biology, revealed possible resistance mechanisms of the host bacterium such as mutations in LPS and spermidine biosynthesis and can also be used to characterize unknown gene products in P. aeruginosa.

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Section: Resultsmentioning

confidence: 99%

“…Characterization of phages is based on morphology as well as on combined genomic and proteomic approaches [9-12]. Other publications describe the host range of phages, which is important with regard to phage therapy [13-15]. …”

Section: Introductionmentioning

confidence: 99%

Sequencing and Characterization of Pseudomonas aeruginosa phage JG004

et al. 2011

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“…Of note were the interesting differences in the effectiveness of infiltration of bird organs by different types of phages injected at the same doses. Intraperitoneal injection of 10 11 PFU of phages (4 phages were tested) into mice resulted in a blood concentration of 5 × 10 8 –2 × 10 10 PFU × ml –1 two hours after injection, which indicates the effective infiltration of the inner environment of the organism [112]. One of the earlier (but also one of the most rigorously performed) studies of the phage pharmacokinetics [113] showed the effective infiltration of Shigella dysenteriae bacteriophages through the mouse’s hematoencephalic barrier.…”

Section: The Pharmacokinetics Of Phage Preparationsmentioning

confidence: 99%

“…Mice that received intraperitoneal doses of phage [112] had very quick increases in blood phage titer (up to 10 10 PFU × ml –1 ), after which the titer decreased approximately by a factor of 10 3 after 12 hours and continued to decrease in a soft curve. The authors approximated this two–phase curve using the following equation: С = 3.525 × 10 9 × e –0,753t + 2.35 × 10 7 × e –0,0997t , where С is the concentration expressed in PFU × ml –1 ; t is the time, in hours; while the numeric parameters varied for the different types of phages.…”

Section: The Distribution Of Phage Particles In the Organism And Theimentioning

confidence: 99%

“…Phages survive slightly longer in the spleen [2, 102, 116]. It seems that the reticuloendothelial system plays a major role in this process as opposed to the circulating phagocytes, since mice with cyclophosphamide–induced neutropenia exhibit only limited inhibition of phage elimination [112]. …”

Section: The Distribution Of Phage Particles In the Organism And Theimentioning

confidence: 99%

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Ecological Basis for Rational Phage Therapy

2010

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Understanding the mutual interactions of bacterial and phage populations in the environment of a human or animal body is essential in any attempt to influence these complex processes, particularly for rational phage therapy. Current knowledge on the impact of naturally occurring bacteriophages on the populations of their host bacteria, and their role in the homeostasis maintenance of a macro host, is still sketchy. The existing data suggest that different mechanisms stabilize phage–bacteria coexistence in different animal species or different body sites. The defining set of parameters governing phage infection includes specific physical, chemical, and biological conditions, such as pH, nutrient densities, host prevalence, relation to mucosa and other surfaces, the presence of phage inhibiting substances, etc. Phage therapy is also an ecological process that always implies three components that form a complex pattern of interactions: populations of the pathogen, the bacteriophages used as antibacterial agents, and the macroorganism. We present a review of contemporary data on natural bacteriophages occuring in human– and animal–body associated microbial communities, and analyze ecological and physiological considerations that determine the success of phage therapy in mammals.

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Pharmacokinetics and Biodistribution of Phages and their Current Applications in Antimicrobial Therapy

Kang,

Bagchi,

Chen

2023

Advanced Therapeutics

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Antimicrobial resistance remains a critical global health concern, necessitating the investigation of alternative therapeutic approaches. With the diminished efficacy of conventional small molecule drugs due to the emergence of highly resilient bacterial strains, there is growing interest in the potential for alternative therapeutic modalities. As naturally occurring viruses of bacteria, bacteriophage (or phage) are being re‐envisioned as a platform to engineer properties that can be tailored to target specific bacterial strains and employ diverse antibacterial mechanisms. However, limited understanding of key pharmacological properties of phage is a major challenge to translating its use from preclinical to clinical settings. Here, this work reviews modern advancements in phage‐based antimicrobial therapy and discusses the in vivo pharmacokinetics and biodistribution of phage, addressing critical challenges in their application that must be overcome for successful clinical implementation.

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Blood kinetics of four intraperitoneally administered therapeutic candidate bacteriophages in healthy and neutropenic mice

Cited by 28 publications

References 12 publications

Sequencing and Characterization of Pseudomonas aeruginosa phage JG004

Sequencing and Characterization of Pseudomonas aeruginosa phage JG004

Ecological Basis for Rational Phage Therapy

Pharmacokinetics and Biodistribution of Phages and their Current Applications in Antimicrobial Therapy

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