Table 3.

Phages as antibacterial or anti-biofilm agents relative to producers of antibiotics.

Property of Anti-biofilm Agent	As Considered in Terms of Bacteriophages	As Considered in Terms of Antibiotic Producers
Inherent predators of bacteria	Particularly for obligately lytic phages, their ability to replicate is closely associated with their ability to kill target bacteria, resulting in an antibacterial activity which is under strong selection, as evidenced by all lytic phages obligately killing target bacteria to produce new phage virions	Particularly for organisms that are not obligate predators of bacteria, their reproduction likely is not explicitly dependent on an ability to kill bacteria, suggesting that antibiotic production is not under as strong selection in non-predatory organisms as it is for predatory ones
Obligate predators of bacteria	The concept that losing a meal is less costly than becoming a meal, to explain differential selective pressures acting on predators versus prey [129], is less applicable to organisms that tend to die if they fail to succeed in exploiting a given meal, once obtained, and this tends to be the case for parasites and, by extension, for phages, i.e., as host-killing parasites	For antibiotic-producing organisms, the cost associated with an antibiotic being less efficacious likely is lower than the equivalent costs to phages for less than optimal antibacterial activity because ongoing replication of antibiotic-producing organisms mostly is not absolutely dependent on inhibition of target bacteria metabolism
Concentration of antibacterial activity within the vicinity of individual target bacteria	Antibacterial action tends to be concentration dependent, as too can be antibacterial toxicity, and phages are able to concentrate their antibacterial activity not just in the vicinity of target bacteria, but within target bacteria	Concentration of antibiotics on specific targets can be more difficult to achieve for organisms that release antibiotics randomly in all directions and/or for which antibiotic release is not triggered by contact with target organisms
Concentration of antibacterial activity within spatially associated groups of target bacteria	An ability to replicate in the course of effecting antibacterial activity can allow phages to concentrate their activity spatially within phage-sensitive microcolonies or phage-sensitive cellular arrangements	Antibiotic-producing organisms also are capable of replication, including in the vicinity of target organisms, though replication by binary fission can be slower than that achievable by phages in the presence of high target-bacteria densities
Bactericidal activity	For lytic phages the death of target bacteria tends to be highly associated with antibacterial activity	Even among effective antibiotics, not all result directly in the death of target bacteria, i.e., bacteriostatic agents
Lytic activity	For lytic phages the lysis of target bacteria is highly associated with antibacterial activity and can lead to sequential removal of biofilm material (e.g., leading to “Active penetration” [120])	Not all antibiotics give rise directly to the lysis of target bacteria so therefore do not necessarily directly give rise to destruction of biofilm physical structure
EPS depolymerases	Certain phages deploy enzymes that are capable of breaking down biofilm extracellular matrix	Antibiotics in and of themselves will not likely possess EPS depolymerase functions
Single-hit killing kinetics	Generally the death of sensitive bacteria follows the adsorption of only a single phage	Generally the death of sensitive bacteria requires exposure to large numbers of molecules of individual antibiotic types