Exploring the therapeutic potential of staphylococcal phage formulations: Current challenges and applications in phage therapy

Abstract

Unconstrained consumption of antibiotics throughout the expanse of the 21st century has resulted in increased antimicrobial resistance (AMR) among bacterial pathogens, a transpiring predicament affecting the public healthcare sector. The upsurge of multidrug-resistant pathogens, including Staphylococcus aureus, synchronously with the breakdown of the conventional antibiotic pipeline has led to the exploration of alternate strategies. Phage therapy applications have thus gained immense prominence among the scientific community to conquer this notorious pathogen associated with wide-ranging clinical manifestations, especially in immunosuppressed individuals. In this direction, a plethora of phage formulations like topical solutions, medicated dressings impregnated with phages, liposomal entrapments, etc., have been considered as an effective and upcoming strategy. Owing to the synergistic effect of phages with other antibacterial agents, they can be easily exploited for biomedical application. This review primarily focuses on the therapeutic implications of S. aureus phages in the biotechnological and medical arena. Through this review article, we have also discussed the current status and the incurring challenges in phage therapy.

Gentamicin Augments the Quorum Quenching Potential of Cinnamaldehyde In Vitro and Protects Caenorhabditis elegans From Pseudomonas aeruginosa Infection

“…The pathogenicity of P. aeruginosa primarily depends on the production of diverse virulence factors, including destructive enzymes, secondary metabolites, toxins, siderophores, and resilient biofilms that are stringently regulated by its intricate QS mechanisms ( Moradali et al., 2017 ). The last decade has seen an unprecedented increase in AMR globally, underscoring the need for developing alternative intervention strategies to existing antimicrobial regimens ( Khullar et al., 2022 ). In this direction, targeting the bacterial QS systems to attenuate pathogen virulence has gained momentum amongst scientists, paving the way for innovating novel anti-virulence therapies ( Chadha et al., 2021a ).…”

The Medicinal Phage—Regulatory Roadmap for Phage Therapy under EU Pharmaceutical Legislation

“…The phages would be therapeutically non-handleable in this undosed form. Instead, depending on the infection [ 101 ], the phages need to be prepared with additional excipients (Article 1(3b) of Directive 2001/83/EC) into the required dosage form. Within a medicinal product, phages are thus active substances within the meaning of Article 1(3a) of Directive 2001/83/EC, whereby an active substance is “ any substance or mixture of substances intended to be used in the manufacture of a medicinal product and that, when used in its production, becomes an active ingredient of that product intended to exert a pharmacological, immunological or metabolic action […].”…”

“…The dosage form of the phage-containing medicinal product depends, among other things, on the infection site (internal, external, local, or systemic). Possible dosage forms under investigation include the incorporation of phages into gels, ointments, gauze, or liquid solutions for injection [ 14 , 77 , 96 , 101 , 102 , 103 , 104 , 105 ]. In addition, inhalable phage therapeutics are being developed for the treatment of respiratory diseases [ 71 , 106 , 107 ].…”

Phage engineering and phage‐assisted CRISPR‐Cas delivery to combat multidrug‐resistant pathogens

“…Many of the strategies involve encapsulating or entrapping the phages within liposomes, fibers, and hydrogels. 159,[162][163][164] Liposomes are enclosed lipid bi-layered nanostructures, spherical in shape, and hollow, allowing them to carry aqueous solutions. Bacteriophages enclosed by liposomes have been shown to protect the phages against host environmental insults such as acidic pH and degrading enzymes found in the stomach and gut, respectively.…”

“…To overcome this hurdle, much research is being focused on devising delivery strategies that could allow bacteriophages to reach to the target site and exhibit their full potential. Many of the strategies involve encapsulating or entrapping the phages within liposomes, fibers, and hydrogels 159,162–164 …”