title: Hurdles in bacteriophage therapy: deconstructing the parameters.
abstract: Bacterial infections in animals impact our food production, leading to economic losses due to food rejection and the need for preventive and curative measures. Since the onset of the antibiotic era, the rise of antibiotic-resistant pathogens is causing scares in health care and food producing facilities worldwide. In the search of new therapeutics, re-evaluation of bacteriophage (phage) therapy, using naturally occurring bacterial viruses to tackle infections, is gaining interest. Many studies report about phage therapy success, showing the value and power of these natural viruses. Although phages carry some interesting traits and their basic biology is now well understood, this review argues that phage therapy has not revealed all of its secrets and many parameters remain understudied, making the outcome of phage therapy highly variable depending on the disease incidence. These difficulties include poorly understood mechanisms of phage penetration and distribution throughout the body, the variable expression and accessibility of phage receptors on the bacterial host in in vivo conditions and the unusual (non-linear) phage pharmacokinetics. These parameters are not easily measured in realistic in vivo settings, but are nevertheless important hurdles to overcome the high variability of phage therapy trials. This critical approach is in accordance with Goethe's statement; "Difficulties increase the nearer we get to the goal". However, since the importance of the goal itself also rises, both difficulties and goal justify the need for additional in depth research in this domain.
authors: Viral Genetics Research Group, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium; Structural and Molecular Microbiology, VIB, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium; Department Structural Biology, VIB, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium; Laboratory of Gene Technology, KU Leuven, Kasteelpark Arenberg 21, 3001 Leuven, Belgium. Electronic address: jessica.tsonos@gmail.com.
authors: Jessica
authors: J
authors: Tsonos
authors: Laboratory of Gene Technology, KU Leuven, Kasteelpark Arenberg 21, 3001 Leuven, Belgium. Electronic address: dieter.vandenheuvel@biw.kuleuven.be.
authors: Dieter
authors: D
authors: Vandenheuvel
authors: Laboratory of Gene Technology, KU Leuven, Kasteelpark Arenberg 21, 3001 Leuven, Belgium. Electronic address: yves.briers@biw.kuleuven.be.
authors: Yves
authors: Y
authors: Briers
authors: Structural and Molecular Microbiology, VIB, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium; Department Structural Biology, VIB, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. Electronic address: hdegreve@vub.ac.be.
authors: Henri
authors: H
authors: De Greve
authors: Viral Genetics Research Group, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. Electronic address: jphernal@vub.ac.be.
authors: Jean-Pierre
authors: JP
authors: Hernalsteens
authors: Laboratory of Gene Technology, KU Leuven, Kasteelpark Arenberg 21, 3001 Leuven, Belgium. Electronic address: rob.lavigne@kuleuven.be.
authors: Rob
authors: R
authors: Lavigne
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000628:therapy* / Q000821:virology; D001433:Bacteriolysis; D001435:Bacteriophages / Q000235:genetics*; D001691:Biological Therapy / Q000379:methods / Q000639:trends / Q000662:veterinary*; D005260:Female; D005523:Food Supply; D011991:Receptors, Virus / Q000378:metabolism; D056189:Viral Tropism / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D011991:Receptors, Virus
keywords: Phage kinetics; Phage therapy; Phage translocation; State of bacteria in vivo