Bacteriophage proteins as antimicrobials to combat antibiotic resistance

Abstract

Bacterial infections associated with multidrug resistance are among the leading causes of death and represent a major threat to the human health of the new millennium. Several pathogenic bacteria have become resistant to several antibiotic classes, and strains resistant to all available antibiotics already exist. Therefore, in an era of the rise of multidrug-resistant superbugs, and where solutions are becoming scarce, there is an urgent need to find alternative and effective antibacterial agents. Bacteriophages, the viruses of microbes, due to their bacterial predatory nature represent a natural toolbox on promising antibacterial proteins. Here, we describe the most promising proteins (virion-associated lysins [VALs], endolysins, polysaccharide depolymerases, and holins) that can be used to treat bacterial infections, including those associated with high antibiotic resistance. The biological features and studies that demonstrate the therapeutic effectiveness of these enzymes on pathogens are demonstrated. The VALs and endolysins are enzymes with the ability to degrade the bacterial peptidoglycan (thereby compromising and lysing the cells) and are the most well-studied phage proteins with several successful studies reported in vitro and in vivo. There are however other promising phage-derived enzymes that target bacteria with a different mode of action. Polysaccharide depolymerases do not kill bacteria, but instead degrade their extracellular polymers that protect the cells from the environment. They have been found to be particularly useful to control bacterial infections in cooperation with the host immune system. Finally, the holins are also emerging as a new class of antibacterials. These enzymes permeabilize the inner bacterial membranes making holes on them, and although only few reports have demonstrated its antibacterial activity, their potential use as therapeutic agents is expected to be high. This chapter demonstrates the hidden antimicrobial potential of the phage proteome, with specific examples of phage-derived proteins that can be used to control drug-resistant bacterial infections.