Fate of Bacteriophage Particles Introduced into Mice by Various Routes.

Keller, R.; Engley, Frank B.

doi:10.3181/00379727-98-24112

Cited by 66 publications

(74 citation statements)

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“…Per os delivery also was possible, with the introduction of phages into the GI tract of mice resulting in virions circulating into the blood. 60 See reference 61 for a recent review and discussion of phage transfer from the human gut to the blood.…”

Section: Phage Treatment Of Human Infectionsmentioning

confidence: 99%

Phage treatment of human infections

et al. 2011

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Phages as bactericidal agents have been employed for 90 years as a means of treating bacterial infections in humans as well as other species, a process known as phage therapy. In this review we explore both the early historical and more modern use of phages to treat human infections. We discuss in particular the little-reviewed French early work, along with the Polish, US, Georgian and Russian historical experiences. We also cover other, more modern examples of phage therapy of humans as differentiated in terms of disease. In addition, we provide discussions of phage safety, other aspects of phage therapy pharmacology, and the idea of phage use as probiotics.

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Section: Phage Treatment Of Human Infectionsmentioning

confidence: 99%

Phage treatment of human infections

et al. 2011

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“…They were identified as the major sites of phage accumulation in early studies. Phage titers are usually the highest there, even higher than in the blood . After systemic delivery, phages can reach spleen and liver within minutes and attain relatively high titers within 1 to 3 hours .…”

Section: Traveling Inside the Systemmentioning

confidence: 99%

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

Dąbrowska

2019

Medicinal Research Reviews

228

212

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Bacteriophages are not forgotten viruses anymore: scientists and practitioners seek to understand phage pharmacokinetics in animals and humans, investigating bacteriophages as therapeutics, nanocarriers or microbiome components. This review provides a comprehensive overview of factors that determine phage circulation, penetration, and clearance, and that in consequence determine phage applicability for medicine. It makes use of experimental data collected by the phage community so far (PubMed 1924‐2016, including non‐English reports), combining elements of critical and systematic review. This study covers phage ability to enter a system by various routes of administration, how (and if) the phage may access various tissues and organs, and finally what mechanisms determine the courses of phage clearance. The systematic review method was applied to analyze (i) phage survival in the gut (gut transit) and (ii) phage ability to enter the mammalian system by many administration routes. Aspects that have not yet been covered by a sufficient number of reports for mathematical analysis, as well as mechanisms underlying trends, are discussed in the form of a critical review. In spite of the extraordinary diversity of bacteriophages and possible phage applications, the analysis revealed that phage morphology, phage specificity, phage dose, presence of sensitive bacteria or the characteristics of treated individuals (age, taxonomy) may affect phage bioavailability in animals and humans. However, once phages successfully enter the body, they reach most organs, including the central nervous system. Bacteriophages are cleared mainly by the immune system: innate immunity removes phages even when no specific response to bacteriophages has yet developed.

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“…administration). Keller and Engley (1958) showed that after oral administration of 4 × 10 9 pfu of Bacillus megaterium 899a phage to mice the phage could be detected in blood of most of the mice after 5 min and in urine after 30 min. However, they could not confirm the presence of the phage in blood in 14% of mice.…”

Section: Introductionmentioning

confidence: 99%

Means to Facilitate the Overcoming of Gastric Juice Barrier by a Therapeutic Staphylococcal Bacteriophage A5/80

et al. 2017

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In this article we compare the efficacy of different pharmacological agents (ranitidine, and omeprazole) to support phage transit from stomach to distal portions of the gastrointestinal tract in rats. We show that a temporal modification of environment in the animal stomach may protect Twort-like therapeutic antistaphylococcal phage A5/80 (from bacteriophage collection of the Hirszfeld Institute of Immunology and Experimental Therapy PAS in Wroclaw, Poland) from the inactivation by gastric juice effectively enough to enable a significant fraction of orally administered A5/80 to pass to the intestine. Interestingly, we found that yogurt may be a relatively strong in enhancing phage transit. Given the immunomodulating activities of phages our data may suggest that phages and yogurt can act synergistically in mediating their probiotic activities and enhancing the effectiveness of oral phage therapy. We also demonstrate that orally applied phages of similar size, morphology, and sensitivity to acidic environment may differ in their translocation into the bloodstream. This was evident in mice in which a therapeutic staphylococcal phage A5/80 reached the blood upon oral administration combined with antacid agent whilst T4 phage was not detected even when applied in 103 times higher dose. Our findings also suggest that phage penetration from digestive tract to the blood may be species-specific.

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Fate of Bacteriophage Particles Introduced into Mice by Various Routes.

Cited by 66 publications

References 0 publications

Phage treatment of human infections

Phage treatment of human infections

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

Means to Facilitate the Overcoming of Gastric Juice Barrier by a Therapeutic Staphylococcal Bacteriophage A5/80

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