Bacteriophages and Phage-Derived Enzymes as Antibacterial Agents

Dear Colleagues,

The discovery of antibiotics has changed modern medicine. They have become one of the most effective weapons in the fight against bacterial infections. We have learned to obtain them from microorganisms and fungi and synthesize them de novo. Since 1928, when Fleming managed to isolate the active substance from mold called penicillin, to the present day, over a hundred of them have been discovered. As early as 1945, Fleming warned the world that the overuse of antibiotics would lead to the emergence of resistant forms of bacteria. Bacterial resistance to antibiotics did not appear with their use by humans. It has existed for millions of years and is an evolutionary adaptation of microorganisms to living in different environments. By currently using antibiotics in unlimited quantities, we provoke bacteria to defend themselves against them and produce resistant forms. The massive appearance of pathogenic strains of bacteria resistant to most or even all known antibiotics has been called “the antibiotic crisis”. Therefore, there is an urgent need to develop new antibacterial agents and novel approaches to fight against pathogenic bacteria.

In the era of such serious problems, we have forgotten about the existence of a cheap and effective way to combat bacterial infections, which is phage therapy. More than 100 years have passed since bacteriophages were discovered. They were commonly used to combat bacterial infections such as dysentery or gangrene. Bacteriophages multiply only on bacteria and are characterized by high specificity, which means that they develop, in general, in one species of bacteria and often only in one strain of bacteria. They multiply as long as they have access to their host, so when they lyse bacteria that are sensitive to them, they stop multiplying. They are a self-replicating drug; it is enough to administer a small amount of phages during a massive bacterial infection for them to multiply to a high titer. Due to the fact that phages are very specific to a given strain of bacteria, they should be selected individually for each infection. Then we will be sure that they will work and, most importantly, that they do not destroy the patient's bacterial flora. This is undoubtedly their great advantage. During antibiotic therapy, the intestinal microbiota is seriously reduced, and in such conditions, bacteria and pathogenic fungi begin to multiply. Phage therapy must meet certain conditions to be effective. Phage preparations should be perfectly purified so as not to cause allergic reactions (remnants of bacterial cells on which the phages were multiplied may remain). The genomes of phages used for therapy must be sequenced so that we are certain that they do not carry toxin genes or any other genes encoding compounds that are dangerous to the patient. Of course, bacteria defend themselves against phage infection by creating resistant forms, which is why we must remember this so as not to make the same mistakes as with antibiotic therapy. We can avoid the formation of phage-resistant bacteria if we use not one phage but a mixture of several phages, which we call a phage cocktail, to combat a given bacterial strain.

Bacteriophages used for phage therapy should be lytic, which means that after entering the bacterial cell, phage genetic material should multiply in it and not be incorporated into its genome. Pathogenic bacteria often create higher-order structures at the site of infection, which are resistant to disinfectants, ultraviolet radiation, and antibiotics. They have been called biofilms. Phage therapy seems to be one of the most effective methods of removing them at the moment. Bacteria most often create biofilms on smooth surfaces made of glass or stainless steel, so they appear in various devices in hospitals and also in machines in food industry production lines. Since biofilm-forming bacteria are resistant to all disinfectants and antibiotics, the only way to remove them is mechanically. Unfortunately, this method does not give good results because biofilms grow back quickly. Using phages, phage-derived enzymes, or those in combination with other agents, such as nanomaterials, could solve the problem.

Since therapy based on the use of bacteriophages and phage-derived enzymes is under development, there is a need for further studies in this area. This Special Issue is devoted to these topics. Both original papers and review articles are welcome, provided they are within the scope of this Special Issue. We invite all researchers working in the field of the use of phages and enzymes encoded by these viruses in combating pathogenic bacteria to submit their works.

Prof. Dr. Grzegorz Wegrzyn
Guest Editor

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• phage therapy
• lytic bacteriophages
• phage-derived enzymes
• antibiotic resistance