Efficacy of Phage- and Bacteriocin-Based Therapies in Combatting Nosocomial MRSA Infections

Abstract

Staphylococcus aureus is a pathogen commonly found in nosocomial environments where infections can easily spread - especially given the reduced immune response of patients and large overlap between personnel in charge of their care. Although antibiotics are available to treat nosocomial infections, the increased occurrence of antibiotic resistance has rendered many treatments ineffective. Such is the case for methicillin resistant S. aureus (MRSA), which has continued to be a threat to public health since its emergence. For this reason, alternative treatment technologies utilizing antimicrobials such as bacteriocins, bacteriophages (phages) and phage endolysins are being developed. These antimicrobials provide an advantage over antibiotics in that many have narrow inhibition spectra, enabling treatments to be selected based on the target (pathogenic) bacterium while allowing for survival of commensal bacteria and thus avoiding collateral damage to the microbiome. Bacterial resistance to these treatments occurs less frequently than with antibiotics, particularly in circumstances where combinatory antimicrobial therapies are used. Phage therapy has been well established in Eastern Europe as an effective treatment against bacterial infections. While there are no Randomized Clinical Trials (RCTs) to our knowledge examining phage treatment of S. aureus infections that have completed all trial phases, numerous clinical trials are underway, and several commercial phage preparations are currently available to treat S. aureus infections. Bacteriocins have primarily been used in the food industry for bio-preservation applications. However, the idea of repurposing bacteriocins for human health is an attractive one considering their efficacy against many bacterial pathogens. There are concerns about the ability of bacteriocins to survive the gastrointestinal tract given their proteinaceous nature, however, this obstacle may be overcome by altering the administration route of the therapy through encapsulation, or by bioengineering protease-resistant variants. Obstacles such as enzymatic digestion are less of an issue for topical/local administration, for example, application to the surface of the skin. Bacteriocins have also shown impressive synergistic effects when used in conjunction with other antimicrobials, including antibiotics, which may allow antibiotic-based therapies to be used more sparingly with less resistance development. This review provides an updated account of known bacteriocins, phages and phage endolysins which have demonstrated an impressive ability to kill S. aureus strains. In particular, examples of antimicrobials with the ability to target MRSA strains and their subsequent use in a clinical setting are outlined.

Antibacterial Peptides Resistance in Staphylococcus aureus: Various Mechanisms and the Association with Pathogenicity

“…Bacterial AMPs are also called bacteriocins. Some of these antibacterial peptides and bacteriocins were also shown to be effective against MRSA [12][13][14] and have potential applications in the clinic [15,16]. Therefore, these peptides are attracting attention as candidates for next-generation antibacterial chemotherapeutic agents because of their high stability and the establishment of purification methods in recent years.…”

Staphylococcus aureus—A Known Opponent against Host Defense Mechanisms and Vaccine Development—Do We Still Have a Chance to Win?

“…As the world rightly focuses on limiting the spread of COVID-19, the current pandemic situation has exposed our vulnerability to the infections for which there are no effective vaccines or treatments [105,106]. An integrated strategy that includes multitargeted vaccines together with modern diagnostic tools, novel antibiotics, monoclonal antibodies, microbiota modulation, as well as the use of antimicrobial peptides, bacteriocins, plantderived products and bacteriophages are required to combat AMR effectively [119][120][121][122][123][124]. The still-developing research trend concerning interference with the expression of pathogen virulence factors at the molecular and submolecular levels is also very important.…”

Development of Antibiofilm Therapeutics Strategies to Overcome Antimicrobial Drug Resistance

“…A phage lysin has proven to be efficacious in eradicating biofilms by fundamentally cleaving the bacterial cell and also effective towards persister cells. Recombinant exebacase (Lysin CF-301) for treatment of MRSA endocarditis and bacteraemia in synergism with some antibiotics is now in clinical trials [218][219][220]. The stumbling block with macrophage treatment is the resistance formed and their swift clearance by the host immune response.…”