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Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the...
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Bacteriophages, or phages, are viruses that specifically infect bacteria, utilizing their genetic material to hijack host cellular machinery for replication. DNA bacteriophages employ single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) genomes. These phages exhibit diverse replication strategies and host interactions, influencing their ecological roles and applications in biotechnology and medicine.ssDNA BacteriophagesssDNA phages, with their small genomes, utilize unique strategies to...
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In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
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In Vivo Bacteriophage Biodistribution.

Nicolas Dufour1,2,3, Raphaëlle Delattre1,3,4, Laurent Debarbieux5

  • 1Department of Microbiology, Molecular Biology of Gene in Extremophiles, Institut Pasteur, 25 Rue du Docteur Roux, 75015, Paris, France.

Methods in Molecular Biology (Clifton, N.J.)
|November 10, 2017
PubMed
Summary

Bacteriophage therapy requires pharmacokinetic data, like conventional drugs, to optimize dosing and reduce toxicity. This study outlines methods for determining bacteriophage biodistribution and elimination in vivo.

Keywords:
BacteriophageBacteriophage therapyClearanceHalf-lifePharmacokineticVolume of distribution

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Area of Science:

  • Microbiology
  • Pharmacology
  • Biotechnology

Background:

  • Bacteriophage therapy is experiencing a resurgence as a potential antibacterial treatment.
  • Widespread acceptance of bacteriophages necessitates understanding their pharmacokinetic profiles, similar to conventional pharmaceuticals.
  • Pharmacokinetic data are crucial for optimizing bacteriophage therapy efficacy and safety in clinical applications.

Purpose of the Study:

  • To outline fundamental methods for experimentally determining bacteriophage pharmacokinetic parameters.
  • To provide examples of data calculation for key in vivo pharmacokinetic parameters of bacteriophages.
  • To support the clinical integration of bacteriophage therapy by providing essential pharmacokinetic data.

Main Methods:

  • Experimental determination of bacteriophage concentrations in biological matrices over time.
  • Application of pharmacokinetic modeling to analyze biodistribution and elimination data.
  • Calculation of key parameters such as half-life, volume of distribution, and clearance.

Main Results:

  • Established methodologies for acquiring essential bacteriophage pharmacokinetic data.
  • Demonstrated calculations for determining in vivo biodistribution and elimination parameters.
  • Provided a framework for understanding bacteriophage behavior within a host organism.

Conclusions:

  • Understanding bacteriophage pharmacokinetics is essential for their successful application in antibacterial therapy.
  • The described methods and calculations facilitate the optimization of bacteriophage dosing regimens.
  • This work contributes to the broader acceptance and clinical utility of bacteriophage-based treatments.