Table 1.

Comparison of bacteriophages and endolysins as antimicrobials.

Selected properties	Bacteriophage	Endolysin
Specificity and host range	Generally specific to one bacterial species (or strains within a species). Limited impact on microbiota composition.	Narrow or broad depending on the chemical structure of the targeted macromolecule. Limited impact on microbiota composition.
Mode of action	Bacteriolytic activity depends on the titer, multiplicity of infection (MOI), burst size and propagation rate.	Bacteriolytic activity depends on concentration and minimum inhibitory concentration (MIC).
Resistance development	Resistance developed by mutation, receptor modification, passive adaptation, restriction-modification, CRISPR-Cas, pseudolysogeny.	Bacteria are less likely to develop resistance to endolysins.
Stability	Stability properties dependent on structural protein composition.	Endolysins have a short half-life, but effectively work in short duration due to the rapid mode-of-action.
Antibiofilm activity	Relatively effective with limited penetration capacity.	Effective against biofilms with higher penetration capacity.
Inflammatory response	Reticuloendothelial system (RES) clearance and immunogenic.	Immunogenic, induction of antibody production.
Pharmacokinetics	Not properly defined, self-replicating and can be cleared by immune system.	Evaluated in some endolysins; chemical structure affects penetration, plasma protein binding, and proteolysis degradation.
Combined therapy	Synergistic effect possible such as: phage cocktails, phage-protein and antibiotic–phage–protein combination.	Synergistic effect between two endolysins with different catalytic specificities or between an endolysin and an antibiotic.