Ecological Basis for Rational Phage Therapy

Abstract

Understanding the mutual interactions of bacterial and phage populations in the environment of a human or animal body is essential in any attempt to influence these complex processes, particularly for rational phage therapy. Current knowledge on the impact of naturally occurring bacteriophages on the populations of their host bacteria, and their role in the homeostasis maintenance of a macro host, is still sketchy. The existing data suggest that different mechanisms stabilize phage–bacteria coexistence in different animal species or different body sites. The defining set of parameters governing phage infection includes specific physical, chemical, and biological conditions, such as pH, nutrient densities, host prevalence, relation to mucosa and other surfaces, the presence of phage inhibiting substances, etc. Phage therapy is also an ecological process that always implies three components that form a complex pattern of interactions: populations of the pathogen, the bacteriophages used as antibacterial agents, and the macroorganism. We present a review of contemporary data on natural bacteriophages occuring in human– and animal–body associated microbial communities, and analyze ecological and physiological considerations that determine the success of phage therapy in mammals.

Phage treatment of human infections

“…The story of Russia's role in the development of phage therapy is long, inaccessible to the non-Russian speaker, and has not been subject to the same kind of scrutiny as has the Georgian experience. Due to limitations in both space and access to resources, we only briefly outline the Russian story here and include a 103 gives insight into some of the more recent thought and work. See also various English-language reviews by Viktor Krylov.…”

“…The result of treatment was elimination of the target bacteria from prostatic fluid. Letarov et al 103 note that rectal phage suppositories are available on the Russian market. Slopek et al 64 report 92.9% positive cases for phage treatment of 42 "Diseases of the genitourinary tract".…”

“…An additional issue that interfered with wide consideration of this work stemmed similarly from phages representing a standard of care, resulting in a tendency in many (but not all) publications to not compare phage treatments with phage-less controls but instead, for example, to compare the efficacy of one phage formulation with each other. A major Soviet pharmacological giant, Microgen, has now taken over all of the commercial phage production in Russia, and a wide variety of their phage preparations are available in pharmacies as well as on line, 3,103 and, reportedly, are used extensively in many parts of Russia. However, they seem to have published little in terms of phage characterization or clinical trials.…”

Phage Therapy: Eco-Physiological Pharmacology

“…See Figure 6 for facile illustration of how particularly it is ecological interactions, as mediated through the physiologies associated with multiple organisms that give rise to the pharmacology associated with phage therapy. See also Letarov et al [107] for a complementary treatment of eco-physiological issues as they pertain to phage therapy. For general overviews of various aspects of phage ecology as well as phage impact on bacteria, see Abedon [108, 109].…”

“…and also whether any physical blocks on virion movement are present, including, for example, anatomical divisions between compartments as found in animals. These latter distribution issues are complex, varying as a function of phage properties, the site being treated, how phages are applied, and the extent to which disease as well as medical intervention may modify phage movement within bodies; see, for example, [85, 93, 107, 111, 112]. …”