Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics

Jończyk‐Matysiak, Ewa; Weber‐Dąbrowska, Beata; Owczarek, Barbara; Międzybrodzki, Ryszard; Łusiak-Szelachowska, Marzanna; Łodej, Norbert; Górski, Andrzej

doi:10.3390/v9060150

Cited by 68 publications

(58 citation statements)

References 82 publications

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“…Thus, when reaching systemic circulation, phages not only are diluted, but also can be immediately captured or filtered, probably by the mononuclear phagocyte system (MPS; older term: reticuloendothelial system, RES), as proposed by the early researchers and confirmed later . Other blood cells that have been proposed as able to bind bacteriophages are erythrocytes; nevertheless, their contribution to possible capturing and circulating of phage particles is not well documented and remains unclear.…”

Section: Traveling Inside the Systemmentioning

confidence: 99%

“…127,129,138,141,143 Thus, when reaching systemic circulation, phages not only are diluted, but also can be immediately captured or filtered, probably by the mononuclear phagocyte system (MPS; older term: reticuloendothelial system, RES), as proposed by the early researchers and confirmed later. 19,127,[144][145][146] Other blood cells that have been proposed as able to bind bacteriophages are erythrocytes 147…”

Section: Phages In the Bloodmentioning

confidence: 99%

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

Dąbrowska

2019

Medicinal Research Reviews

247

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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Section: Traveling Inside the Systemmentioning

confidence: 99%

Section: Phages In the Bloodmentioning

confidence: 99%

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

Dąbrowska

2019

Medicinal Research Reviews

247

212

View full text Add to dashboard Cite

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“…However, the emergence of rapid culture‐independent bacterial detection/identification techniques should circumvent this disadvantage. Phages also can act as antigens, especially in the case of systemic infections, and thus may evoke undesired immunological reactions such as phage inactivation . The use of a different phage type can then in a second instance provide a solution. Moreover, phages can be inactivated for instance by leukocytes and other nonspecific blood factors, as well as by gastric juices and by antiseptics . Therefore, the use of alkalinizing agents such as sodium bicarbonates is introduced as pre‐phage application …”

Section: Reborn Worldwide and Western Interests And Doubts About Phagmentioning

confidence: 99%

A century of bacteriophage research and applications: impacts on biotechnology, health, ecology and the economy!

Vandamme

Mortelmans

2018

J of Chemical Tech & Biotech

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About a century ago, bacteriophages or phages – viruses that infect bacteria – were discovered and reported in the scientific literature. This review aims at a comprehensive survey of bacteriophage discovery, research and applications since the 1920s, and its impact on molecular biology, biotechnology, health, ecology and the economy. Phage therapy has been proven a valuable asset to deal with pathogenic bacterial infections since the early 1920s, and has been practiced ever since, especially in the former Soviet Union and in Eastern Europe. The Western world remained sceptical and resorted to the widespread use of antibiotics since the 1940s. Now that antibiotic resistance among pathogenic bacteria has spread alarmingly and few really novel antibiotic compounds are in the pipeline, renewed attention is being directed to the use of phages as antibacterial agents in medicine. Because of this renewed interest in phage therapy in the Western world, novel applications with phages are being pursued in the human health, environmental and the agri‐food sectors. This review will focus on (1) the history of early phage use and its successes and problems, (2) the study of phages as important tools in the development of molecular biology and biotechnology, (3) current developments in phage research including the use of phage endolysins for use in antibacterial treatment, (4) phage production systems including undesirable phage contamination of industrial fermentation processes based on bacteria, (5) recent applications in phage therapy and in phage‐based control, and (6) the roles of phages in nature and in the human gut. © 2018 Society of Chemical Industry

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“…Molecular imaging of the cells containing GFP phage particles confirmed that the phage particles were successfully ingested by the dendritic cells . In addition, dendritic cells were more sensitive and responsive upon uptake of active virion particles than that of synthetic particles . Following the ingestion of the phages, another study using macrophages confirmed phage degradation within splenocytes, which ended up in macrophage compartments .…”

Section: Phage Therapymentioning

confidence: 87%

“…113 In addition, dendritic cells were more sensitive and responsive upon uptake of active virion particles than that of synthetic particles. 114,115 Following the ingestion of the phages, another study using macrophages confirmed phage degradation within splenocytes, which ended up in macrophage compartments. 116 These findings suggest that the immune system cannot be infected by and is able to get rid of the phage particles.…”

Section: Phage Therapy and The Human Immune Systemmentioning

confidence: 99%

Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy

Jariah

Hakim

2019

Reviews in Medical Virology

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Summary Phages and bacteria are known to undergo dynamic and co‐evolutionary arms race interactions in order to survive. Recent advances from in vitro and in vivo studies have improved our understanding of the complex interactions between phages, bacteria, and the human immune system. This insight is essential for the development of phage therapy to battle the growing problems of antibiotic resistance. It is also pivotal to prevent the development of phage‐resistance during the implementation of phage therapy in the clinic. In this review, we discuss recent progress of the interactions between phages, bacteria, and the human immune system and its clinical application for phage therapy. Proper phage therapy design will ideally produce large burst sizes, short latent periods, broad host ranges, and a low tendency to select resistance.

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Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics

Cited by 68 publications

References 82 publications

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

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

A century of bacteriophage research and applications: impacts on biotechnology, health, ecology and the economy!

Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy

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