Abstract

Pseudomonas aeruginosa is a frequent participant in wound infections. Emergence of multiple antibiotic resistant strains has created significant problems in the treatment of infected wounds. Phage therapy (PT) has been proposed as a possible alternative approach. Infected wounds are the perfect place for PT applications, since the basic condition for PT is ensured; namely, the direct contact of bacteria and their viruses. Plenty of virulent (“lytic”) and temperate (“lysogenic”) bacteriophages are known in P. aeruginosa. However, the number of virulent phage species acceptable for PT and their mutability are limited. Besides, there are different deviations in the behavior of virulent (and temperate) phages from their expected canonical models of development. We consider some examples of non-canonical phage-bacterium interactions and the possibility of their use in PT. In addition, some optimal approaches to the development of phage therapy will be discussed from the point of view of a biologist, considering the danger of phage-assisted horizontal gene transfer (HGT), and from the point of view of a surgeon who has accepted the Hippocrates Oath to cure patients by all possible means. It is also time now to discuss the possible approaches in international cooperation for the development of PT. We think it would be advantageous to make phage therapy a kind of personalized medicine.

Highlights

  • Gram-negative bacteria of species Pseudomonas aeruginosa may be found in different natural habitats, because they adapt to different conditions

  • The original idea of phage therapy is based on the assumption that interactions of phages and bacteria are similar with predator-prey relationships and the development of virulent phage proceeds within the framework of the lytic cycle

  • Studies of bacteriophages in laboratories are usually accomplished under conditions which are optimal for bacterial host growth

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Summary

Introduction

Gram-negative bacteria of species Pseudomonas aeruginosa may be found in different natural habitats, because they adapt to different conditions. The creation of such an organization requires support on an inter-state level, because its development goes beyond the possibilities of individual researchers or research laboratories, and apparently requires coordination on a number of different levels The existence of such a system could play a positive role in quick reactions to the occurrence of local epidemics, such as the emergence of the outbreak caused by an enterohemorrhagic (EHEC) strain of E. coli serotype O104: H4 in early May. 2011 in northern Germany, or in the case of the outbreak of listeriosis in September and October 2011 in the U.S.A. In the U.S.A., for instance, there is a phage mixture active against Listeria (integrated drug ListShieldTM; [36]) which is permitted by the US Food and Drug Administration for use in. Phage therapy at some future time could be included into the arsenal of personalized medicine

Non-Canonical Interaction of Phages and Bacteria
Some Examples of Reasons for Pseudolysogenic Conditions
Pseudolysogeny in the Case of phiKZ-Like Phages
Pseudovirulence
Growth of Phages in the Presence of Plasmids
Possibilities for the Emergence of New Phages in the Course of Phage Therapy
Transposable Phages
Phage F116
Evidence for Migrations of phiKZ-Like Phages
Optimizing the Selection of Phages for Therapy
10.1. The Properties of a New Bacteriophage CHU Pseudomonas aeruginosa
10.2. Properties of a New Bacteriophage TL
14. Future Therapeutic Phages
Findings
Isolation and analysis of hybrid phages D3112 and B39
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