Beata Weber-Dabrowska

Bacteriophage penetration in vertebrates

Bacteriophages are viruses that infect bacteria. They are the most numerous life forms on earth. As antibiotic resistance is becoming an increasingly worldwide challenge, bacteriophages as potential antimicrobial agents are being more intensively explored. Some very important questions involve their ability to penetrate higher organisms, as this determines potential phage activity in antibacterial treatment. Higher organisms are widely exposed to bacteriophages, which penetrate them quite freely. Bacteriophage activity can be influenced by specific antibodies which, together with the nonspecific immune system, can contribute to their rapid clearance from the organism. Bacteriophages can also interact directly with mammalian cells and even play a role in the development of some nonbacterial diseases, although they are not able to multiply in these cells. All aspects of the interaction between phages and higher organism are of interest and importance for further medical and biochemical applications.

Bacteriophage Therapy of Bacterial Infections: An Update of our Institute’s Experience

1307 patients with suppurative bacterial infections caused by multidrug-resistant bacteria of different species were treated with specific bacteriophages (BP). BP therapy was highly effective; full recovery was noted in 1123 cases (85.9%). In 134 cases (10.9%) transient improvement was observed and only in 50 cases (3.8%) was BP treatment found to be ineffective. The results confirm the high effectiveness of BP therapy in combating bacterial infections which do not respond to treatment with the available antibiotics.

The potential role of endogenous bacteriophages in controlling invading pathogens

Abstract.Bacteriophages (phages) are omnipresent in our environment, and recent studies highlight their potential impact on the microbial world. Phages can also be present in mammalian organisms, including man (intestines, oral cavity, urine, sputum and serum). Data are available which suggest that those endogenous phages could play an important role in eliminating bacteria and regulating the body ecosystem. Furthermore, our most recent findings suggest that phages can exert immunosuppressive action in the gut, helping control local inflammatory and autoimmune reactions, and demonstrate anticancer activity. We hypothesize that phages could act in concert with the immune system in immunosurveillance against bacteria, viruses and cancer.

New insights into the possible role of bacteriophages in host defense and disease

BackgroundWhile the ability of bacteriophages to kill bacteria is well known and has been used in some centers to combat antibiotics – resistant infections, our knowledge about phage interactions with mammalian cells is very limited and phages have been believed to have no intrinsic tropism for those cells.Presentation of the hypothesisAt least some phages (e.g., T4 coliphage) express Lys-Arg-Gly (KGD) sequence which binds β3 integrins (primarily αIIbβ3). Therefore, phages could bind β3+ cells (platelets, monocytes, some lymphocytes and some neoplastic cells) and downregulate activities of those cells by inhibiting integrin functions.Testing the hypothesisBinding of KGD+ phages to β3 integrin+ cells may be detected using standard techniques involving phage – mediated bacterial lysis and plaque formation. Furthermore, the binding may be visualized by electron microscopy and fluorescence using labelled phages. Binding specificity can be confirmed with the aid of specific blocking peptides and monoclonal antibodies. In vivo effects of phage – cell interactions may be assessed by examining the possible biological effects of β3 blockade (e.g., anti-metastatic activity).Implication of the hypothesisIf, indeed, phages can modify functions of β3+ cells (platelets, monocytes, lymphocytes, cancer cells) they could be important biological response modifiers regulating migration and activities of those cells. Such novel understanding of their role could open novel perspectives in their potential use in treatment of cardiovascular and autoimmune disease, graft rejection and cancer.

Bacteriophage therapy for infections in cancer patients

Abstract Cancer patients are known to be immunocompromised and susceptible to infections. We have used bacteriophages matched for specific bacterial isolates, to treat antibiotic-resistant infections in those patients. Cure of infection was achieved in all cases, indicating very high efficacy of bacteriophage therapy.

The potential of phage therapy in bacterial infections of the eye.

Antibiotic resistance has become a major health challenge which poses a significant threat, also in ophthalmology. For example, methicillin-resistant Staphylococcus aureus may cause dramatic complications, including bilateral blindness as a consequence of orbital cellulitis and panophthalmitis. This menace has provoked a greatly revived interest in phage therapy. In recent years, a number of papers have been published suggesting its efficacy in animal and human bacterial infections, but none of them addressed the phage potential in ophthalmology, which is the subject of this mini review.

Influence of Bacteriophage Preparations on Intracellular Killing of Bacteria by Human Phagocytes in Vitro

Bacteriophages are viruses that infect bacteria. It was shown that bacteriophage therapy is an effective method of combating bacterial infections, including infections caused by antibiotic-resistant bacterial strains. One of the main obstacles to widespread use of phage preparations is limited knowledge regarding the influence of bacteriophages on human organisms. In our study, we evaluated whether application of phage preparations impair bactericidal activities of human phagocytes (granulocytes and monocytes). In our study, we used preparations of phages T2 and T4 specific to Escherichia coli and A3 phage specific to Staphylococcus aureus. We found that bacteriophage preparations do not influence intracellular killing of bacteria by human phagocytes. The effect is irrespective of phage preparation type (lysate, purified phage preparation), phage titer of the preparation, and whether bacteria phagocytosed by phagocyte cells are sensitive or insensitive to phage (bacteriophages homologous and heterologous to bacteria). Although the results of our study are preliminary, they support previous data indicating safety of therapeutic application of phages.