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[Phage therapy, an alternative to antibiotic therapy?)].

ABSTRACT: Bacteriophages are viruses that infect and parasitize bacteria. They can present a lytic cycle that determines the lysis of the infected bacteria. Each phage is specific to a particular bacterial genus or species. The current increase in the incidence of antibiotic resistance in human bacteria has favored the study of phages as a therapeutic alternative (phage therapy). Previous studies have shown the efficacy of these elements in cutaneous and intestinal infections. Different clinical trials are underway to establish the safety, reactogenicity and therapeutic efficacy of multiple phage. Being active elements, phages must undergo rigorous quality controls to ensure the absence of undesirable effects. The bacterial lysis that they cause is of a magnitude inferior to the one provoked by the antibiotics. As problems to be solved in the future are the possibility of using mixtures of several phages, establish the ideal route of administration and modify them genetically to deactivate bacterial resistance genes.

SUBMITTER: Reina J

PROVIDER: S-EPMC6159377 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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[Phage therapy, an alternative to antibiotic therapy?)].

Reina J J Reina N N

Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia 20180216 2

Bacteriophages are viruses that infect and parasitize bacteria. They can present a lytic cycle that determines the lysis of the infected bacteria. Each phage is specific to a particular bacterial genus or species. The current increase in the incidence of antibiotic resistance in human bacteria has favored the study of phages as a therapeutic alternative (phage therapy). Previous studies have shown the efficacy of these elements in cutaneous and intestinal infections. Different clinical trials ar ...[more]

PMID: 29451376

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Project description:When phages infect bacteria cultured in the presence of sublethal doses of antibiotics, the sizes of the phage plaques are significantly increased. This phenomenon is known as phage-antibiotic synergy (PAS). In this study, the observation of PAS was extended to a wide variety of bacterium-phage pairs using different classes of antibiotics. PAS was shown in both Gram-positive and Gram-negative bacteria. Cells stressed with β-lactam antibiotics filamented or swelled extensively, resulting in an increase in phage production. PAS was also sometimes observed in the presence of other classes of antibiotics with or without bacterial filamentation. The addition of antibiotics induced recA expression in various bacteria, but a recA deletion mutant strain of Escherichia coli also showed filamentation and PAS in the presence of quinolone antibiotics. The phage adsorption efficiency did not change in the presence of the antibiotics when the cell surfaces were enlarged as they filamented. Increases in the production of phage DNA and mRNAs encoding phage proteins were observed in these cells, with only a limited increase in protein production. The data suggest that PAS is the product of a prolonged period of particle assembly due to delayed lysis. The increase in the cell surface area far exceeded the increase in phage holin production in the filamented host cells, leading to a relatively limited availability of intracellular holins for aggregating and forming holes in the host membrane. Reactive oxygen species (ROS) stress also led to an increased production of phages, while heat stress resulted in only a limited increase in phage production.IMPORTANCE Phage-antibiotic synergy (PAS) has been reported for a decade, but the underlying mechanism has never been vigorously investigated. This study shows the presence of PAS from a variety of phage-bacterium-antibiotic pairings. We show that increased phage production resulted directly from a lysis delay caused by the relative shortage of holin in filamented bacterial hosts in the presence of sublethal concentrations of stress-inducing substances, such as antibiotics and reactive oxygen species (ROS).

Project description:The appearance of bacteria resistant to most or even all known antibiotics has become a serious medical problem. One such promising and effective alternative form of therapy may be the use of phages, the administration of which is considered to be safe and highly effective, especially in animals with drug-resistant infections. Although there have been no reports to date suggesting that bacteriophages can cause any severe complications or adverse effects, we still know little about their interactions with animal organisms, especially in the context of the functioning of the immune system. Therefore, the aim of the present study was to compare the impact of the application of selected bacteriophages and antibiotics (enrofloxacin and colistin), commonly used in veterinary medicine, on immune functions in Salmonella enterica serovar Typhimurium-infected chickens. The birds were infected with S. Typhimurium and then treated with a phage cocktail (14 days), enrofloxacin (5 days), or colistin (5 days). The concentrations of a panel of pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, IL-8, and IL-12) and cytokines that reveal anti-inflammatory effects (IL-10 and IL-4), the percentage of lymphocytes, and the level of stress hormones (corticosterone and cortisol), which significantly modulate the immune responses, were determined in different variants of the experiment. The phage cocktail revealed anti-inflammatory effects when administered either 1 day after infection or 2 days after S. Typhimurium detection in feces, as measured by inhibition of the increase in levels of inflammatory response markers (IL-1β, IL-6, IFN-γ, IL-8, and IL-12). This was also confirmed by increased levels of cytokines that exert an anti-inflammatory action (IL-10 and IL-4) following phage therapy. Moreover, phages did not cause a negative effect on the number and activity of lymphocytes’ subpopulations crucial for normal immune system function. These results indicate for the first time that phage therapy not only is effective but also can be used in veterinary medicine without disturbing immune homeostasis, expressed as cytokine imbalance, disturbed percentage of key immune cell subpopulations, and stress axis hyperactivity, which were observed in our experiments as adverse effects accompanying the antibiotic therapy.

Dataset Information

[Phage therapy, an alternative to antibiotic therapy?)].

Publications

[Phage therapy, an alternative to antibiotic therapy?)].

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