ABSTRACT

This alarming spread of resistance to classic antimicrobial agents has driven the search for new antimicrobials that are broadly effective and less likely to induce AMR.

Bacteriophages (phages), bacterial cell wall hydrolases (BCWHs), and antimicrobial peptides (AMPs) are some of the promising antimicrobial alternatives (Parisien et  al., 2008). Bacteriophages are highly specic and can be active against a single strain of bacteria. Therefore, using bacteriophage against infecting strains was suggested to control undesirable bacterial species in mucosal systems. This approach was rst developed in the last century and showed much potential; however, it also aroused much controversy and concern (Gillor et al., 2008). BCWHs are enzymes that degrade peptidoglycan (major bacterial cell wall component) due to their lytic enzymatic activities, that is, attacking specic sites in the peptidoglycan network, leading to hydrolysis and consequently bacteriolysis (Masschalck and Michiels, 2003). Though they are well established, safe, and efcient against antibiotic-resistant bacteria, the main obstacle to use them for clinical application is the high production costs and not being effective on most gram-negative bacteria due to the presence of outer membrane (Parisien et al., 2008).