Therapeutic Phages as Modulators of the Immune Response: Practical Implications.

While the medical community awaits formal proof of the efficacy of phage therapy, as is required by evidence-based medicine, existing data suggest that phages could also be applied based on their non-antibacterial action, especially phage-mediated immunomodulation. Promising avenues have been revealed by findings indicating that phages may mediate diverse actions in the immune system, while the list of phages able to dampen the aberrant immunity associated with a variety of disorders continuously grows. Here we summarize what is known in this field and possible options for the future.

Pharmacokinetic and Pharmacodynamic Obstacles for Phage Therapy From the Perspective of Clinical Practice.

Bacteriophages present unique features that enable targeted killing of bacteria, including strains resistant to many antibiotics. However, phage pharmacokinetics and pharmacodynamics constitute much more complex and challenging aspects for researchers than those attributable to antibiotics. This is because phages are not just chemical substances, but also biological nanostructures built of different proteins and genetic material that replicate within their bacterial hosts and may induce immune responses acting as simple antigens.

How Interest in Phages Has Bloomed into a Leading Medical Research Activity in Poland.

Poland has a leading position in phage therapy, as reflected by the number of patients treated and relevant publications in quality journals. The Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences was established by Ludwik Hirszfeld, a prominent microbiologist and serologist who also initiated studies on phages and pioneered the activities that set into motion phage therapy at the Institute. To achieve this goal, Hirszfeld had to overcome many difficulties in a post-war Poland.

Do Anti-Phage Antibodies Persist after Phage Therapy? A Preliminary Report.

Phages are immunogenic and may evoke an immune response following their administration. Consequently, patients undergoing phage therapy (PT) produce phage-neutralizing serum antibodies. The clinical significance of this phenomenon for the success or failure of the therapy is currently unclear.

A Thorough Synthesis of Phage Therapy Unit Activity in Poland-Its History, Milestones and International Recognition.

The year 2020 marked 15 years of the Phage Therapy Unit in Poland, the inception of which took place just one year after Poland's accession to the European Union (2004). At first sight, it is hard to find any connection between these two events, but in fact joining the European Union entailed the need to adapt the regulatory provisions concerning experimental treatment in humans to those that were in force in the European Union. These changes were a solid foundation for the first phage therapy center in the European Union to start its activity.

Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far.

Bacteriophages (phages) may be used as an alternative to antibiotic therapy for combating infections caused by multidrug-resistant bacteria. In the last decades, there have been studies concerning the use of phages and antibiotics separately or in combination both in animal models as well as in humans. The phenomenon of phage-antibiotic synergy, in which antibiotics may induce the production of phages by bacterial hosts has been observed.

Phage therapy of wound-associated infections.

Phages are viruses which can specifically infect bacteria, resulting in their destruction. Bacterial infections are a common complication of wound healing, and experimental evidence from animal models demonstrates promising potential for phage-dependent eradication of wound-associated infections. The studies discussed suggest that phage therapy may be an effective treatment, with important advantages over some current antibacterial treatments.

Bronisława Fejgin (1883-1943): Forgotten Important Contributor to International Microbiology and Phage Therapy.

Bronisława Brandla Fejgin was a Polish-born Jewish female physician. Among Fejgin's numerous articles in the field of microbiology, her later work was almost entirely devoted to phage research. Although not equally famous as the phage pioneers from Western Europe, F.

Potential for Phages in the Treatment of Bacterial Sexually Transmitted Infections.

Bacterial sexually transmitted infections (BSTIs) are becoming increasingly significant with the approach of a post-antibiotic era. While treatment options dwindle, the transmission of many notable BSTIs, including , , and continues to increase. Bacteriophage therapy has been utilized in Poland, Russia and Georgia in the treatment of bacterial illnesses, but not in the treatment of bacterial sexually transmitted infections.

Immune Response to Therapeutic Staphylococcal Bacteriophages in Mammals: Kinetics of Induction, Immunogenic Structural Proteins, Natural and Induced Antibodies.

Bacteriophages are able to affect the human immune system. Phage-specific antibodies are considered as major factors shaping phage pharmacokinetics and bioavailability. So far, general knowledge of phage antigenicity nevertheless remains extremely limited.

Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections.

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low.

The Rationale for Using Bacteriophage to Treat and Prevent Periprosthetic Joint Infections.

Prosthetic joint infection (PJI) is a devastating complication after a joint replacement. PJI and its treatment have a high monetary cost, morbidity, and mortality. The lack of success treating PJI with conventional antibiotics alone is related to the presence of bacterial biofilm on medical implants.

Therapeutic Perspectives and Mechanistic Insights of Phage Therapy in Allotransplantation.

Bacterio(phages) are bacteria-infecting viruses that employ host translation machinery to replicate, and upon cell lysis, release new particles into the environment. As a result, phages are prey-specific, thus making targeted phage therapy (PT) possible. Indeed, pre- and posttransplant bacterial infections pose a substantial risk to allograft recipients in their clinical course.

Phage Therapy: Towards a Successful Clinical Trial.

While phage therapy carried out as compassionate use (experimental therapy) has recently flourished, providing numerous case reports of supposedly healed patients, clinical trials aiming to formally prove their value in accord with current regulatory requirements have failed. In light of the current issue of increasing antibiotic resistance, the need for a final say regarding the place of phage therapy in modern medicine is evident. We analyze the possible factors that may favor success or lead to the failure of phage therapy: quality of phage preparations, their titer and dosage, as well as external factors that could also contribute to the outcome of phage therapy.

Phage Prevalence in the Human Urinary Tract-Current Knowledge and Therapeutic Implications.

Recent metagenomic analyses imply an immense abundance of phages in the human body. Samples collected from different sites (lungs, skin, oral cavity, intestines, ascitic fluid, and urine) reveal a generally greater number of phage particles than that of eukaryotic viruses. The presence of phages in those tissues and fluids reflects the paths they must overcome in the human body, but may also relate to the health statuses of individuals.

Sepsis, Phages, and COVID-19.

Phage therapy has emerged as a potential novel treatment of sepsis for which no decisive progress has been achieved thus far. Obviously, phages can help eradicate local bacterial infection and bacteremia that may occur in a syndrome. For example, phages may be helpful in correcting excessive inflammatory responses and aberrant immunity that occur in sepsis.

Treatment of recurrent urinary tract infections in a 60-year-old kidney transplant recipient. The use of phage therapy.

We would like to demonstrate the difficulty of treatment in a patient after kidney transplantation (KTX) who developed chronic urinary tract infection (UTI) with a multi-drug resistant ESBL-producing Klebsiella pneumoniae. The patient underwent several treatment interventions including supportive therapy with bacteriophages. This article presents a case of a 60-year-old patient after KTX repeatedly admitted to the hospital with recurrent UTIs caused by ESBL-producing Klebsiella pneumoniae showing variable susceptibility to carbapenems and full susceptibility to colistin only.

Phage Therapy in Poland - a Centennial Journey to the First Ethically Approved Treatment Facility in Europe.

Although phage discovery is an unquestionable merit of the English bacteriologist Frederick W. Twort and the Canadian-French microbiologist Félix d'Hérelle, who both discovered phages over 100 years ago, the Polish history of phage studies also dates back to those years. In contrast to the Western world, developing phage treatment in Poland has never been abandoned despite the country's tense history marked by the Second World War (WWII) and the communism era.

Natural and Induced Antibodies Against Phages in Humans: Induction Kinetics and Immunogenicity for Structural Proteins of PB1-Related Phages.

Bacteriophages may induce specific antibodies after natural exposure to phages or after phage therapy. As such, phage-specific antibodies might impact phage bioavailability , although limited non-neutralizing or insignificant effects have also been reported. Here, we report antibody induction against PB1-related phages ( viruses LMA2, F8, DP1) in mice over an 80-day period, for a healthy population of humans, and in patients undergoing phage therapy (oral and/or topical treatment).

Factors determining phage stability/activity: challenges in practical phage application.

: Phages consist of nucleic acids and proteins that may lose their activity under different physico-chemical conditions. The production process of phage formulations may decrease phage infectivity. Ingredients present in the preparation may influence phage particles, although preparation and storage conditions may also cause variations in phage titer.