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.

Isolation and phenotypic characterization of bacteriophage SA14 with lytic- and anti-biofilm activity against multidrug-resistant Enterococcus faecalis

“…The age of the biofilm could have impacted the treatment process. In younger biofilms, exopolymeric components are more easily degraded by phages due to the high bacterial cell density and the rapid phage dispersion in the biofilm structure [50]; however, older biofilms prevent the phage from entering the core layers due to the formed thick matrix [51].…”

Activity of Phage–Lactoferrin Mixture against Multi Drug Resistant Staphylococcus aureus Biofilms

“…Bacteriophages are an effective tool against biofilms formed by nosocomial, which are often multi-drug-resistant, strains of bacteria [ 20 , 21 ]. This has been proven by numerous studies by various research groups [ 8 , 22 , 23 ].…”

“…This was also observed by other research groups. Singh et al [ 21 ] and Ammons et al [ 37 ] have reported that the addition of lactoferrin to the medium prevented Pseudomonas aeruginosa from forming biofilms. Additionally, Quinteiri et al [ 17 ] have observed that application of 2.5 mg/mL lactoferrin hydrolysate solution on biofilms attached to glass surfaces caused biofilm dispersion.…”

Nanomedicine against biofilm infections: A roadmap of challenges and limitations

“…This section aims to contextualize the reader providing a concise description of the primary approaches currently employed or under investigation for treating established biofilms, categorized according to their mechanisms of action, and Figure 2 illustrates them. Detailed description can be found in Asma et al, 2022 and Singh, Padmesh, et al, 2022 (Asma et al, 2022; Singh, Amod, et al, 2022). In addition, a list with some examples and references including more detailed information about specific biofilm treatment strategies is presented in Table 1.…”