The Perfect Bacteriophage for Therapeutic Applications—A Quick Guide

Abstract

The alarming spread of multiresistant infections has kick-started the quest for alternative antimicrobials. In a way, given the steady increase in untreatable infectious diseases, success in this endeavor has become a matter of life and death. Perhaps we should stop searching for an antibacterial panacea and explore a multifaceted strategy in which a wide range of compounds are available on demand depending on the specific situation. In the context of this novel tailor-made approach to combating bacterial pathogens, the once forgotten phage therapy is undergoing a revival. Indeed, the compassionate use of bacteriophages against seemingly incurable infections has been attracting a lot of media attention lately. However, in order to take full advantage of this strategy, bacteria’s natural predators must be taken from their environment and then carefully selected to suit our needs. In this review, we have explored the vast literature regarding phage isolation and characterization for therapeutic purposes, paying special attention to the most recent studies, in search of findings that hint at the most efficient strategies to identify suitable candidates. From this information, we will list and discuss the traits that, at the moment, are considered particularly valuable in phages destined for antimicrobial therapy applications. Due to the growing importance given to biofilms in the context of bacterial infections, we will dedicate a specific section to those characteristics that indicate the suitability of a bacteriophage as an antibiofilm agent. Overall, the objective is not just to have a large collection of phages, but to have the best possible candidates to guarantee elimination of the target pathogens.

New Genus Fibralongavirus in Siphoviridae Phages of Staphylococcus pseudintermedius

“…Considering the clinical background and presence of virulence factors in the genome of propagating strain 625, a different, safer propagating strain would be needed for the application of phages in therapy. The use of phages that contain integrase for phage therapy is unfavourable [83], however the described phage QT1 is active against clinical strains of S. pseudintermedius and could be used until a polyvalent phage is described and can be used as a gene source for enzybiotics.…”

Bacteriophage Therapy: Developments and Directions

“…Key elements of the design of fixed phage cocktails to provide the necessary host range breadth, efficacy and durability have been described [34,37,[54][55][56][57] and include: (a) selection of phages with overlapping host ranges; (b) selection of phages with safe genomic characteristics; (c) selection of phages that infect the same host using different receptors; (d) selection of phages that infect using receptors with a high fitness cost for the host to mutate (resulting in a low resistance rate); (e) selection of phages with anti-biofilm activity; (f) selection of phages that synergize with treatment antibiotics, (g) selection of phages that are non-immunogenic; (h) selection of phages with extended half-life in the therapy recipient (long circulating); (i) selection of phages that are suitable for manufacturing and long-term stability. The chief challenge in designing phage cocktails to have lasting efficacy is in addressing resistance in the bacterial host, since through millions of years of coevolution the host has an array of resistance mechanisms [58], resistance is likely to be encountered during phage therapy [59] but can be overcome using rigorous rational cocktail formulation [56], with combinations of phages optimized to minimize resistance [60].…”

Yersinia Phages and Food Safety

“…In addition, their contamination can be caused by the manufacture or processing of the product [4]. For the successful application of phages in food safety, various factors should be taken into consideration, which have been reviewed extensively [74][75][76][77][78][79]. Mainly, the phages should be strongly lytic, stable within the environment they are to be used in, and have a broad host range (alone or in a cocktail) encompassing epidemiologically significant strains.…”