The current status of phage therapy and its advancement towards establishing standard antimicrobials for combating multi drug-resistant bacterial pathogens

Abstract

Phage therapy; a revived antimicrobial weapon, has great therapeutic advantages with the main ones being its ability to eradicate multidrug-resistant pathogens as well as selective toxicity, which ensures that beneficial microbiota is not harmed, unlike antibiotics. These therapeutic properties make phage therapy a novel approach for combating resistant pathogens. Since millions of people across the globe succumb to multidrug-resistant infections, the implementation of phage therapy as a standard antimicrobial could transform global medicine as it offers greater therapeutic advantages than conventional antibiotics. Although phage therapy has incomplete clinical data, such as a lack of standard dosage and the ideal mode of administration, the conducted clinical studies report its safety and efficacy in some case studies, and therefore, this could lessen the concerns of its skeptics. Since its discovery, the development of phage therapeutics has been in a smooth progression. Concerns about phage resistance in populations of pathogenic bacteria are raised when bacteria are exposed to phages. Bacteria can use restriction-modification, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) defense, or mutations in the phage receptors to prevent phage invasion. Phage resistance, however, is often costly for the bacteria and may lead to a reduction in its virulence. The ongoing competition between bacteria and phage, on the other hand, ensures the emergence of phage strains that have evolved to infect resistant bacteria. A phage can quickly adapt by altering one or more aspects of its mode of infection, evading a resistance mechanism through genetic modifications, or directly thwarting the CRISPR-Cas defense. Using phage-bacterium coevolution as a technique could be crucial in the development of phage therapy as well. Through its recent advancement, gene-editing tools such as CRISPR-Cas allow the bioengineering of phages to produce phage cocktails that have broad spectrum activities, which could maximize the treatment's efficacy. This review presents the current state of phage therapy and its progression toward establishing standard medicine for combating antibiotic resistance. Recent clinical trials of phage therapy, some important case studies, and other ongoing clinical studies of phage therapy are all presented in this review. Furthermore, the recent advancement in the development of phage therapeutics, its application in various sectors, and concerns regarding its implementation are also highlighted here. Phage therapy has great potential and could help the fight against drug-resistant bacterial pathogens.