article · Viruses
Over-prescribing antibiotics has driven antimicrobial resistance, making bacteriophages an attractive specific alternative for treating bacterial infections. Phages produce enzymes including endolysins, exolysins, and depolymerases that degrade bacterial surfaces, cell wall components, and exopolysaccharides, with the capacity to destroy biofilms. Gram-positive targets include peptidoglycan, teichoic acids, and flagella, whilst Gram-negative targets include lipopolysaccharides, pili, and capsules. Bacteria defend against phages through physical barriers like capsules or endogenous mechanisms such as CRISPR-Cas systems. Phage proteins can also stimulate immune responses against specific pathogens and improve susceptibility to existing antibiotics. Genomic engineering of phages and the therapeutic deployment of phage-derived proteins offer pathways to overcome current clinical limitations in treating resistant bacterial infections.
Rising antimicrobial resistance reduces the effectiveness of standard antibiotics, creating an urgent need for alternative treatments. Understanding how bacteriophages and their enzymes recognise, penetrate, and dismantle bacterial cells provides insights into targeted therapies capable of clearing persistent, drug-resistant infections and disrupting stubborn protective bacterial biofilms without harming beneficial microbes.
The findings point to potential therapeutic applications using whole phages, genomically engineered phages, or phage-derived enzymes to treat drug-resistant bacterial infections and eradicate biofilms. Potential end users include clinical healthcare providers and biopharmaceutical developers. However, because this work is a foundational review of biological mechanisms and therapy limitations, practical technologies derived from it remain in the early research and development stage.
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Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to over-prescribing antibiotics. Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. Enzymes such as endolysins, exolysins, endopeptidases, endosialidases, and depolymerases produced by phages interact with bacterial surfaces, cell wall components, and exopolysaccharides, and may even destroy biofilms. Enzymatic cleavage of the host cell envelope components exposes specific receptors required for phage adhesion. Gram-positive bacteria are susceptible to phage infiltration through their peptidoglycan, cell wall teichoic acid (WTA), lipoteichoic acids (LTAs), and flagella. In Gram-negative bacteria, lipopolysaccharides (LPSs), pili, and capsules serve as targets. Defense mechanisms used by bacteria differ and include physical barriers (e.g., capsules) or endogenous mechanisms such as clustered regularly interspaced palindromic repeat (CRISPR)-associated protein (Cas) systems. Phage proteins stimulate immune responses against specific pathogens and improve antibiotic susceptibility. This review discusses the attachment of phages to bacterial cells, the penetration of bacterial cells, the use of phages in the treatment of bacterial infections, and the limitations of phage therapy. The therapeutic potential of phage-derived proteins and the impact that genomically engineered phages may have in the treatment of infections are summarized.
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DOI: 10.3390/v16030478
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