A cocktail of in vitro efficient phages is not a guarantee for in vivo therapeutic results against avian colibacillosis

Tsonos, Jessica; Oosterik, Leon; Tuntufye, Huruma Nelwike; Klumpp, Jochen; Butaye, Patrick; Greve, Henri De; Hernálsteens, Jean-Pierre; Lavigne, Rob; Goddeeris, Bruno

doi:10.1016/j.vetmic.2013.10.021

Cited by 40 publications

(32 citation statements)

References 32 publications

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“…N4-like podoviruses comprise a unique group among bacteriophages because their virions include the giant vRNAP that enters the host-cell during phage infection and, therefore, N4-like phages do not require the host RNA-polymerase for transcription of their early genes [25,33]. Over the last decade, tens of N4-like phages have been discovered and their genomes have been sequenced and characterized [33][34][35][36][37][38][39][40][41][42][43][44][45][46]. They have conserved genome organization, including two large clusters of early-middle and late genes, transcribed in opposite orientations, and a group of usually short ORFs with unknown functions, whose number varies between different N4-like phages.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of a Novel Klebsiella pneumoniae N4-like Bacteriophage KP8

Morozova

Бабкин

Kozlova

et al. 2019

Viruses

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Klebsiella pneumoniae is a common pathogen, associated with a wide spectrum of infections, and clinical isolates of K. pneumoniae often possess multiple antibiotic resistances. Here, we describe a novel lytic N4-like bacteriophage KP8, specific to K. pneumoniae, including its genome, partial structural proteome, biological properties, and proposed taxonomy. Electron microscopy revealed that KP8 belongs to the Podoviridae family. The size of the KP8 genome was 73,679 bp, and it comprised 97 putative open reading frames. Comparative genome analysis revealed that the KP8 genome possessed the highest similarity to the genomes of Enquatrovirus and Gamaleyavirus phages, which are N4-like podoviruses. In addition, the KP8 genome showed gene synteny typical of the N4-like podoviruses and contained the gene encoding a large virion-encapsulated RNA polymerase. Phylogenetic analysis of the KP8 genome revealed that the KP8 genome formed a distinct branch within the clade, which included the members of Enquatrovirus and Gamaleyavirus genera besides KP8. The average evolutionary divergences KP8/Enquatrovirus and KP8/Gamaleyavirus were 0.466 and 0.447 substitutions per site (substitutes/site), respectively, similar to that between Enquatrovirus and Gamaleyavirus genera (0.468 substitutes/site). The obtained data suggested that Klebsiella phage KP8 differs from other similar phages and may represent a new genus within the N4-like phages.

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Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of a Novel Klebsiella pneumoniae N4-like Bacteriophage KP8

Morozova

Бабкин

Kozlova

et al. 2019

Viruses

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“…If so, there will be little need for principles beyond the determination of phage host ranges before deployment as therapeutics. Ability to infect the target strain is obviously a necessary condition, but it need not be sufficient, and as the field has progressed, it has become apparent that not all phages are equivalent in treating acute infections ( Smith and Huggins, 1982 ; Henry et al, 2013 ), and many studies of chronic infections reveal that bacteria are not eliminated by phages, even though clinical symptoms are often reduced ( Scott et al, 2007 ; Hurley et al, 2008 ; El-Shibiny et al, 2009 ; Tsonos et al, 2013b ); treatment of plant infections has also revealed efficacy differences among phages ( Balogh et al, 2010 ). Even more problematic, the literature may be biased toward phage therapy successes ( Tsonos et al, 2013a ), obscuring the extent to which the type of phage or treatment matters to the outcome.…”

Section: Introductionmentioning

confidence: 99%

The habits of highly effective phages: population dynamics as a framework for identifying therapeutic phages

Bull

Gill

2014

Front. Microbiol.

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The use of bacteriophages as antibacterial agents is being actively researched on a global scale. Typically, the phages used are isolated from the wild by plating on the bacteria of interest, and a far larger set of candidate phages is often available than can be used in any application. When an excess of phages is available, how should the best phages be identified? Here we consider phage-bacterial population dynamics as a basis for evaluating and predicting phage success. A central question is whether the innate dynamical properties of phages are the determinants of success, or instead, whether extrinsic, indirect effects can be responsible. We address the dynamical perspective, motivated in part by the absence of dynamics in previously suggested principles of phage therapy. Current mathematical models of bacterial-phage dynamics do not capture the realities of in vivo dynamics, nor is this likely to change, but they do give insight to qualitative properties that may be generalizable. In particular, phage adsorption rate may be critical to treatment success, so understanding the effects of the in vivo environment on host availability may allow prediction of useful phages prior to in vivo experimentation. Principles for predicting efficacy may be derived by developing a greater understanding of the in vivo system, or such principles could be determined empirically by comparing phages with known differences in their dynamic properties. The comparative approach promises to be a powerful method of discovering the key to phage success. We offer five recommendations for future study: (i) compare phages differing in treatment efficacy to identify the phage properties associated with success, (ii) assay dynamics in vivo, (iii) understand mechanisms of bacterial escape from phages, (iv) test phages in model infections that are relevant to the intended clinical applications, and (v) develop new classes of models for phage growth in spatially heterogeneous environments.

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“…Data from experimental animal studies (Biswas et al 2002;Shivaswamy et al 2015), and a considerable volume of published clinical experiences, mostly from Eastern Europe, support the view that bacteriophage therapy can be highly efficacious under a variety of circumstances, including when treating serious bacterial infections caused by organisms resistant to multiple antimicrobial compounds (Verstappen et al 2016). On the other hand, in vitro susceptibility to phage is not always a reliable predictor of in vivo efficacy (Tsonos et al 2014). Considerably more robust evidence is required.…”

Section: The Challenge Of Insufficient High-quality Evidencementioning

confidence: 99%

Bacteriophage therapy for management of bacterial infections in veterinary practice: what was once old is new again

Squires

2018

New Zealand Veterinary Journal

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Bacteriophages (or phages) are naturally-occurring viruses that can infect and kill bacteria. They are remarkably diverse, numerous and widespread. Each phage has a narrow host range yet a large majority of bacteria studied so far play host to bacteriophages, hence the remarkable phage diversity. Phages were discovered just over 100 years ago and they have been used for treatment of bacterial infections in humans and other animals since the 1920s. They have also been studied intensively and this has led to, and continues to lead to, major insights in the fields of molecular biology and recombinant DNA technology, including that DNA is the genetic material, nucleotides are arranged in triplets to make codons, and messenger RNA is needed for protein synthesis. This article begins with a description of bacteriophages and explains why there has recently been a strong resurgence of interest in their clinical use for treatment of bacterial infections, particularly those caused by organisms resistant to multiple antimicrobial compounds. The history of bacteriophage therapy is briefly reviewed, followed by a review and critique of promising but very limited clinical research on the use of bacteriophages to treat bacterial infections in dogs. Other potential veterinary uses and benefits of bacteriophage therapy are also briefly discussed. There are important practical challenges that will have to be overcome before widespread implementation and commercialisation of bacteriophage therapy can be achieved, which are also considered.

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A cocktail of in vitro efficient phages is not a guarantee for in vivo therapeutic results against avian colibacillosis

Cited by 40 publications

References 32 publications

Isolation and Characterization of a Novel Klebsiella pneumoniae N4-like Bacteriophage KP8

Isolation and Characterization of a Novel Klebsiella pneumoniae N4-like Bacteriophage KP8

The habits of highly effective phages: population dynamics as a framework for identifying therapeutic phages

Bacteriophage therapy for management of bacterial infections in veterinary practice: what was once old is new again

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