Bacteriophage treatment as an alternative therapy for multidrug-resistant bacteria

Abstract

Multidrug-resistant (MDR) bacteria constitute one of the most serious global health threats. The increasing incidence rate of bacterial infections caused by MDR strains and the decrease in the number of newly developed antibiotics have prompted the scientific community to search for alternatives. One such alternative is the use of bacteriophages. In this review, we discuss the most critical MDR organisms, including Acinetobacter baumanni, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus The efficacy of phage therapy against MDR bacteria is also discussed. We included studies from the last 10 years that examined the efficacy of phage therapy against MDR pathogens. In addition, this review highlights the effect of bacteriophages against bacterial biofilms. The existing knowledge indicates that phage therapy is a potential therapeutic strategy against MDR bacteria. However, the adverse effects of phage therapy, such as toxicity, and the emergence of phage resistance have not yet been resolved.

Keywords: bacterial infections; bacteriophages; biofilms; multidrug-resistant (MDR) bacteria; phage therapy.

Figure 1

- Mechanisms of antibiotic resistance in Acinetobacter (A. baumannii). Resistance can be conferred in A. baumannii through four main mechanisms; A) producing β-Lactamases that degrade the β-lactam ring; thus, inactivating β-lactam antibiotics. B) Preventing access to antibiotics into the bacterial cell through reducing the outer membrane permeability. C) Pumping antibiotics out of the bacterial cell using efflux pumps. D) Modifying antibiotic’s target via genetic mutations; thus, antibiotic is no longer able to bind to its target.

Figure 2

- Schematic representation of biofilm degradation by bacteriophages and its derived enzymes. Bacteriophages degrade bacterial biofilm by 3 mechanisms; (i) Phage-derived endolysins, which degrades bacterial cell walls. (ii) bacteriophages degrade bacterial cell walls and biofilm matrix. (iii) phage-derived depolymerases as free enzyme or tail spike protein degrade biofilm matrix.