Bacteriophages, phage endolysins and antimicrobial peptides – the possibilities for their common use to combat infections and in the design of new drugs

Abstract

The antibiotic resistance in many pathogenic bacteria has become a major clinical problem, therefore, the necessity arises to search for new therapeutic strategies. The most promising solution lies in bacteriophages, phage endolysins and antimicrobial peptides. The aim of this study is to review the possibilities for the common use of bacteriophages, phage endolysins and antimicrobial peptides, both in the form of combined therapies and new strategies for the production of peptide drugs. Bacteriophages are viruses that specifically infect and destroy pathogenic bacteria by penetration into bacterial cells, causing metabolism disorders and, consequently, cell lysis. Phage-encoded endolysins are bacteriolytic proteins produced at the end of the phage lytic cycle that destroy elements of bacterial cell wall and enable the release of phage progeny from host cells. Antimicrobial peptides (AMPs) constitute an element of the innate immunity of living organisms and are characterized by the activity against a broad spectrum of bacteria. In the literature, there are only a few reports on the direct interaction of bacteriophages, phage endolysins and antimicrobial peptides against pathogenic bacteria. In each of them, a synergistic effect was observed, and Phage-encoded antimicrobial peptides as a specific group of AMPs have were also discussed. Phage-display technique was also reviewed in terms of its applications to produce and deliver biologically active peptides. The literature data also suggest that bacteriophages, phage endolysins and antimicrobial peptides can be used in combined therapy, thus negating many of the limitations resulting from their specificity as a single antimicrobial agent.

Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms

“…Nonetheless, it is likely that, as is the case of other antimicrobials, the existence of synergy will depend on the specific phage-protein combination and the bacterial strain. There are several studies reporting the existence of synergy between either phages or phage lytic proteins with antibiotics 36 – 38 , 41 – 43 . In some cases, such combinations were able to reduce the biofilm population depending on the antibiotic and its concentration.…”

“…Another strategy is the combination of multiple phages targeting different receptors in a single phage preparation, known as a phage cocktail 39 , 40 . Phage lytic enzymes have also been combined with other antimicrobials like antibiotics 41 – 43 or used as part of a multi-enzyme approach by mixing them with depolymerases, which target polysaccharides such as those present in the extracellular matrix of biofilms 44 . However, to our knowledge, no study has found synergistic effects between phages and lytic proteins.…”

Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application

“…PGHs have become extensively studied for 20 years, e.g., [11,15,17,53,54,59,61,[63][64][65]67,69,82,106,[141][142][143][144]148,. They can be easily identified and prepared as pure recombinant proteins and have proven to be efficient in killing bacteria, including multidrug-resistant variants [231][232][233][234].…”

“…Therefore, approximately 20 years ago, researchers started to explore phage-encoded antibacterial enzymes that can overcome some of these phage-therapy limitations. A comparison of the typical attributes of antibiotics, phages, PSDs, and PGHs [ 18 , 24 , 27 , 30 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ] is found in Figure 2 . Importantly, manufacturing PSDs and PGHs should not pose many hurdles since large scale recombinant protein production and purification strategies are well established.…”

“…PGHs have become extensively studied for 20 years, e.g., [ 11 , 15 , 17 , 53 , 54 , 59 , 61 , 63 , 64 , 65 , 67 , 69 , 82 , 106 , 141 , 142 , 143 , 144 , 148 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 ,…”