How Good are Bacteriophages as an Alternative Therapy to Mitigate Biofilms of Nosocomial Infections

Abstract

Bacteria survive on any surface through the generation of biofilms that provide a protective environment to grow as well as making them drug resistant. Extracellular polymeric matrix is a crucial component in biofilm formation. The presence of biofilms consisting of common opportunistic and nosocomial, drug-resistant pathogens has been reported on medical devices like catheters and prosthetics, leading to many complications. Several approaches are under investigation to combat drug-resistant bacteria. Deployment of bacteriophages is one of the promising approaches to invade biofilm that may expose bacteria to the conditions adverse for their growth. Penetration into these biofilms and their destruction by bacteriophages is brought about due to their small size and ability of their progeny to diffuse through the bacterial cell wall. The other mechanisms employed by phages to infect biofilms may include their relocation through water channels to embedded host cells, replication at local sites followed by infection to the neighboring cells and production of depolymerizing enzymes to decompose viscous biofilm matrix, etc. Various research groups are investigating intricacies involved in phage therapy to mitigate the bacterial infection and biofilm formation. Thus, bacteriophages represent a good control over different biofilms and further understanding of phage-biofilm interaction at molecular level may overcome the clinical challenges in phage therapy. The present review summarizes the comprehensive details on dynamic interaction of phages with bacterial biofilms and the role of phage-derived enzymes - endolysin and depolymerases in extenuating biofilms of clinical and medical concern. The methodology employed was an extensive literature search, using several keywords in important scientific databases, such as Scopus, Web of Science, PubMed, ScienceDirect, etc. The keywords were also used with Boolean operator "And". More than 250 relevant and recent articles were selected and reviewed to discuss the evidence-based data on the application of phage therapy with recent updates, and related potential challenges.

Keywords: antibiotic resistance; biofilm; depolymerases; extracellular polymeric substance; mitigating strategy; phage; phage cocktail; phage lysins.