Phage Therapy in Prostatitis: Recent Prospects

Prostatitis has various etiology including bacterial infection and dysregulated immunity; some of its forms remain a serious therapeutic challenge. Inflammation occurs in all forms of this disorder and is proposed to predispose to the development of prostate cancer (PC). There are reports that phage therapy is effective in chronic bacterial prostatitis. Recent findings suggest that phages not only eliminate bacteria, but also mediate immunomodulating (for example, anti-inflammatory) functions. The immunomodulating effects of phages could be beneficial in treating all forms of prostatitis and play some role in the prevention of the development of PC. As the etiological factors contributing to the majority of prostatitis cases remains largely unknown, and management options are often likewise limited, phage therapy merits further research as an attractive therapeutic option given its immunomodulating effects irrespective of the underlying causative factor(s)

The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?

The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested. Furthermore, most phages found at different sites in the human body are temperate, so their therapeutic effects and their potential beneficial effects remain unclear. Hence, far, no correlation has been observed between the presence of widespread crAssphage in the human population and human health and diseases. Here, we emphasize the beneficial effects of phage transfer in fecal microbiota transplantation (FMT) in Clostridioides difficile infection. The safety of phage use in gastrointestinal disorders has been demonstrated in clinical studies. The significance of phages in the FMT as well as in gastrointestinal disorders remains to be established. An explanation of the multifaceted role of endogenous phages for the development of phage therapy is required

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. Interestingly, even a strong anti-phage humoral response does not exclude the success of PT. On the other hand, it cannot be ruled out that phage–antibody complexes may be trapped in tissues and organs causing injury and late complications of PT. Therefore, patients should be monitored for the presence of serum antibodies and therapy discontinued if their level is high. Our preliminary data suggest that the kinetics of the disappearance of those antibodies may vary from patient to patient and in some cases may take more than a year

Bacteriophages in the gastrointestinal tract and their implications

Abstract The gut microbiota plays an essential role in health and disease of humans. Bacteriophages are the most abundant members of the gut virobiota and display great diversity. Phages can translocate through the mucosa to lymph and internal organs and play a role as regulators of the bacterial population in the gut. Increasing abundance of phages in the gut mucosa may reduce colonization by bacteria. Moreover, phages may have an immunomodulatory role in the immune response in the human gut. The role of phages in inflammatory bowel disease (IBD) remains unknown. Phages may take part in the development of IBD, but there are also data suggesting the protective role of phages in the gut of patients with IBD. Furthermore, recent data suggest that phages may mediate the beneficial effects of fecal microbiota transplantation (FMT). Therefore, evidence is accumulating to highlight the protective immunomodulating activity of the gut phages

Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics

Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes—contained in granules—that are potentially toxic proteins. Therefore, it is important to investigate the possible interactions between phages and immune cells and avoid any phage side effects on them. Recent progress in knowledge concerning the influence of phages on phagocytes is also important as such interactions may shape the immune response. In this review we have summarized the current knowledge on phage interactions with phagocytes described so far and their potential implications for phage therapy. The data suggesting that phage do not downregulate important phagocyte functions are especially relevant for the concept of phage therapy

The Potential of Phage Therapy in Sepsis

Sepsis remains a difficult clinical challenge, since our understanding of its immunopathology is incomplete and no efficacious treatment currently exists. Its earlier stage results from an uncontrolled inflammatory response to bacteria while in the later stage disturbed immune response with immunodeficiency syndrome develops. More than a hundred of clinical trials have not provided an efficient therapy which could ascertain an improvement or cure. Recent advancements in immunobiology of bacterial viruses (phages) indicate that in addition to their well-known antibacterial action phages have potent immunomodulating properties. Those data along with preliminary observations in experimental animals and the clinic strongly suggest that clinical trials on the efficacy of phages in sepsis are urgently needed

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 Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum, 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. With the ever-increasing likelihood of antibiotic resistance prevailing and the continuous transmission of BSTIs, alternative treatments must be explored. This paper discusses the potentiality and practicality of phage therapy to treat BSTIs, including Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Streptococcus agalactiae, Haemophilus ducreyi, Calymmatobacterium granulomatis, Mycoplasma genitalium, Ureaplasma parvum, Ureaplasma urealyticum, Shigella flexneri and Shigella sonnei. The challenges associated with the potential for phage in treatments vary for each bacterial sexually transmitted infection. Phage availability, bacterial structure and bacterial growth may impact the potential success of future phage treatments. Additional research is needed before BSTIs can be successfully clinically treated with phage therapy or phage-derived enzymes

Bacteriophage Procurement for Therapeutic Purposes

Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. Herein we attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented