Abstract
Bacteriophages can be used as antibacterial agents as a form of biological control, e.g., such as phage therapy. With active treatment, phages must “actively” produce new virions, in situ, to attain “inundative” densities, i.e., sufficient titers to eradicate bacteria over reasonable timeframes. Passive treatment, by contrast, can be accomplished using phages that are bactericidal but incapable of generating new phage virions in situ during their interaction with target bacteria. These ideas of active versus passive treatment come from theoretical considerations of phage therapy pharmacology, particularly as developed in terms of phage application to well-mixed cultures consisting of physically unassociated bacteria. Here I extend these concepts to bacteria which instead are physically associated. These are bacteria as found making up cellular arrangements or bacterial microcolonies—collectively, clonal bacterial “clumps”. I consider circumstances where active phage replication would be required to effect desired levels of bacterial clearance, but populations of bacteria nevertheless are insufficiently prevalent to support phage replication to bacteria-inundative densities across environments. Clumped bacteria, however, may still support active treatment at more local, i.e., sub-millimeter, within-clump spatial scales, and potential consequences of this are explored mathematically. Application is to the post-harvest biocontrol of foodborne pathogens, and potentially also to precise microbiome editing. Adequate infection performance by phages in terms of timely burst sizes, that is, other than just adsorption rates and bactericidal activity, thus could be important for treatment effectiveness even if bacterial densities overall are insufficient to support active treatment across environments. Poor phage replication during treatment of even low bacterial numbers, such as given food refrigeration during treatment, consequently could be problematic to biocontrol success. In practical terms, this means that the characterization of phages for such purposes should include their potential to generate new virions under realistic in situ conditions across a diversity of potential bacterial targets.
Highlights
Phage therapy is the use of bacterial viruses, i.e., bacteriophages, as antibacterial agents
The first step of successful phage treatment of bacteria is for phage virions which have been added to environments—or which instead have been generated within an environment through phage replication—to encounter bacteria, that is, for virion-bacterium collision to take place
For phage-mediated biocontrol to be effective in eliminating phage-sensitive target bacteria, phages must attain sufficient densities within the vicinity of those bacteria to result in some approximation of 100% of them becoming phage adsorbed
Summary
Phage therapy is the use of bacterial viruses, i.e., bacteriophages, as antibacterial agents. This utility dates to the pre-antibiotic, nearly 100-year-old use of phages in the treatment of infectious diseases with bacterial etiologies [1]. Phage therapy serves as a form of biological control or ―biocontrol‖ of bacteria [4]. Such biocontrol can include the use of phages to combat phytopathogens of crops, the use of phages as disinfectants such as of fomites, or the use of phages to selectively remove undesired bacteria from foods (for a list of reviews of the latter, see the Appendix). Consideration of the dynamics of phage-bacterial interactions, such as during phage-mediated biocontrol of bacteria, has been derived to a substantial extent from that of particle-collision theory
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