Abstract
The resurgence of research into phage biology and therapy is, in part, due to the increasing need for novel agents to treat multidrug-resistant infections. Despite a long clinical history in Eastern Europe and initial success within the food industry, commercialized phage products have yet to enter other sectors. This relative lack of success is, in part, due to the inherent biological limitations of whole phages. These include (but are not limited to) reaching target sites at sufficiently high concentrations to establish an infection which produces enough progeny phages to reduce the bacterial population in a clinically meaningful manner and the limited host range of some phages. Conversely, parallels can be drawn between antimicrobial enzymes derived from phages and conventional antibiotics. In the current article the biological limitations of whole phage-based therapeutics and their derived antimicrobial enzymes will be discussed. In addition, the ability of more complex formulations to address these issues, in the context of medical and non-medical applications, will also be included.
Highlights
Renewed interest in the clinical and non-clinical application of phages and their derived antimicrobial enzymes has been stimulated by the need for new types of antibacterial agents to combat the ongoing problem of antibiotic resistance [1,2,3,4]
Among the key double-edged advantages of therapies is that their specific activity minimizes the collateral damage to commensal microflora at the same time as limiting the host range of each therapy
A synergistic effect was shown by Garcia and colleagues who demonstrated that the combination of the Staphylococcal endolysin LysH5 with Nisin was able to induce synergy and increase the antibacterial activity eight-fold against a single strain of Staphylococcus aureus in a checkerboard minimum inhibitory concentration (MIC) assay and pasteurized milk [104]
Summary
Renewed interest in the clinical and non-clinical application of phages and their derived antimicrobial enzymes has been stimulated by the need for new types of antibacterial agents to combat the ongoing problem of antibiotic resistance [1,2,3,4]. Therapy based upon the application of whole phages has traditionally been utilized in Eastern Europe to treat a variety of different infections ranging from diabetic foot ulcers to stomach complaints This type of treatment takes advantage of the lytic replication cycle of wholly-virulent bacteriophages [10,11]. For therapies based upon whole phages or their derived antimicrobial enzymes, the formulation of biologically-active components with additional adjuncts may address a number of these factors. The current review seeks to investigate the general issues associated with whole phage and phage derived antimicrobial enzymes (in particular endolysins as these are the most widely studied) and how they could be incorporated with compatible adjuncts for clinical and non-clinical applications. Targets Pseudomonas aeruginosa Endolysin that targets S. aureus and MRSA Phage-derived lysin that targets S. aureus blood stream infections
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