Krystyna 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.

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.

Delivering phage therapy per os: benefits and barriers

ABSTRACT Introduction: Multidrug-resistant bacterial infections of the gastrointestinal tract pose a serious public health concern. High levels of antibiotic drug resistance, along with the potential for antibiotics to precipitate disease or alter the gut microbiome has prompted research into alternative treatment methods. Evidence suggests that bacteriophage therapy delivered per os may be well-suited to target such infections. Areas covered: Herein, we discuss the specific advantages and challenges of using orally administered phage therapy. Our literature review encompasses recent works using phages to target various clinically-relevant bacteria in vivo. We also provide insights into methods that aim to overcome the barriers to effective phage transit through the harsh gastrointestinal environment. Expert commentary: Evidence from a number of in vivo animal studies suggests that targeting bacterial infections using phages delivered orally holds potential. Efficacious oral phage therapy depends on the delivery of sufficient phage titers to the infection site, which may be hindered by the host’s gastrointestinal tract and immune response.