Table 5.
Major Features of Antibiotics, Lytic Bacteriophages and Non-Lytic Phage Proteins as Antimicrobials.
| Selected feature | Antibiotic | Phage | Non-lytic phage protein |
|---|---|---|---|
| Selective toxicity | Active
only on specific microbial metabolism pathway; Inhibition of bacterial toxins production possible |
Propagation on bacterial host (predator-prey relation) | Active
only on specific microbial metabolism pathway; Inhibition of bacterial toxins production possible |
| Antimicrobial spectrum | Broad against Gram- positive and Gram-negative, extra- and intracellular pathogens | Narrow
very specific mostly on one bacterial species; No available phage preparations for intracellular pathogens |
Narrow or broad |
| Influence on normal flora | Dysbiosis; Secondary infection possible |
No influence eradication of targeted strain only | Low influence on gut flora |
| Serious side effects on the host | Allergy, dysbiosis,
secondary infections; Endotoxin (LPS) and other toxins release possible |
Endotoxin (LPS) and other toxins release during cell lysis possible | Endotoxin (LPS) and other toxins release during cell lysis possible |
| Efficient bacterial killing |
Bacteriostatic or bactericidal; Concentration- or time-dependent killing; PAE effect possible (postantibiotic effect); MIC (minimum inhibitory concentration); Effective on growing cells |
Bacteriolytic; Phage titer-dependent killing; Virulence efficacy: MOI, burst size, growth rate; Effective on growing cells |
Bacteriostatic or bacteriolytic; Concentration- dependent killing; MIC (minimum inhibitory concentration); Effective on growing and non-growing cells |
| Penetration to the tissues, concentration, dose, timing of administration | Well defined; Blood flow to tissue; Chemical structure affects penetration and plasma protein binding - effective concentration; Relatively long shelf-life; Concentration at the infection site related on systemic concentration and blood circulation |
Not well defined; Size and capsid protein structure affects systemic concentration regulated by reticuloendothelial system (RES) clearance and immune cellular defense mechanisms; Self-replicating agent - the concentration increase at the infection site |
Not well defined; Blood flow to tissue; Chemical structure affects penetration, plasma protein binding and proteolysis degradation - effective concentration; Concentration at the infection site related on systemic concentration and blood circulation |
| Stability | Well
elaborated; Chemically-stable |
Not much data in current papers | Relatively not stable; |
| Formulations | Easy to administrate - pills, syrups, injections, aerosols, formulas for local application | Liquid phage filtrate, tablets, formulas for local application | Injections, aerosols, formulas for local application |
| Delivery route |
Orally or parenteral route (mostly intravenous) for majority of
infection locations (systemic or topical disease); Locally (topical infections) |
Parenteral route (systemic infections); Orally (gastrointestinal infections); Locally (topical infections) |
Parenteral route (systemic infections); Oral application limited by proteolysis; Locally (topical infections) |
| Resistance development | Vertical - mutation and
selection; Horizontal - acquisition of resistance genes from another organism via transformation, transduction and conjugation Multidrug resistance acquisition possible; High level of induced resistance |
Vertical - mutation and
selection; Temperate phage acquisition; Low level of induced resistance |
Vertical - mutation and
selection; Low level of induced resistance |
| Multidrug therapy | drugs in combined therapy; Prevention of resistance development; Eradication of multidrug resistant strains; Synergistic effect possible |
Cocktail of phages (3-5) or phage-antibiotic
combination; Prevention of resistance development; Extended activity spectrum; Synergistic effect possible |
Combined therapy of protein-protein;
phage-protein; antibiotic-protein; antibiotic-phage-protein; Prevention of resistance development; Extended activity spectrum; Synergistic effect possible |
| Development of new preparation | Antibiotic modification; In silico design possible |
Fast and easy isolation of new phages from environmental source |
In silico development by protein data bases
exploration; Analysis of annotated phage genomes |
| Biofilm eradication | Difficult effective drug concentration in biofilm structure limited; | Relatively effective phage penetration into the biofilm structure possible by means of EPS degradation (phage enzymes) | Effective biofilm degradation possible by EPS degrading phage enzymes |
| Manufacturing | Well elaborated | Limitation in densification and purification; Large scale methods need to be adopted | Relatively simple; Recombinant peptides or synthetic analogues; Large scale methods adopted |