Table 2.

Comparison of the properties of antibiotic, phage, and endolysin as antibacterial therapeutic agents

Properties	Antibiotic	Phage	Endolysin	References
Bacteriocidal specificity	Broad spectrum more common than narrow spectrum	Typically narrow, species or strain specificity	Relatively broad lytic activity	[82, 83]
Proliferation	Non-proliferation	Self-proliferation	Non-proliferation	[11, 84]
Mode of action	Applied from without, target specific sites, typically disrupts one bacterial process	Applied from without, disrupt many essential cellular processes	Applied from without, target bonds in the peptidoglycan	[83, 85]
Bacteriocidal speed	Short time between administration and eradication of bacteria	Long time between administration and eradication of bacteria	Rapid bacterial activity within seconds of contact	[14, 86]
Intracellular activity	Diffusion through membranes allows for treatment of intracellular bacteria	Unable to penetrate eukaryotic cells	Few or modified ones (e.g., CPP-fused endolysins) can enhance intracellular efficacy	[77, 86, 87]
Resistance development	Prone to develop resistance	Resistance occurs quite frequently	No resistance has ever been reported over number of treated generations	[88, 89]
Antibiofilm activity	Not very effective against biofilms	Effective antibiofilm agents with limited penetration	Relatively effective antibiofilm agents with higher destruction of biofilms	[13, 83]
Immune response	Generally non-immunogenic	Interaction with immune systems and susceptible to clearance by antibodies	Immunogenic, lower degree of antibody neutralization	[26, 51, 90]
Pharmacokinetics	Establish the relationship between concentration and the magnitude of killing activity	Little clinical evidence that defines optimal dosages and pharmacokinetic parameters of therapy	Defined concentration at site of infection and in blood circulation	[29, 88, 89]

CPP cell-penetrating peptide