Bacteriophage Adsorption: Likelihood of Virion Encounter with Bacteria and Other Factors Affecting Rates

Abstract

For ideal gasses, the likelihood of collision of two molecules is a function of concentrations as well as environmental factors such as temperature. This too is the case for particles diffusing within liquids. Two such particles are bacteria and their viruses, the latter called bacteriophages or phages. Here, I review the basic process of predicting the likelihoods of phage collision with bacteria. This is a key step governing rates of phage-virion adsorption to their bacterial hosts, thereby underlying a large fraction of the potential for a given phage concentration to affect a susceptible bacterial population. Understanding what can influence those rates is very relevant to appreciating both phage ecology and the phage therapy of bacterial infections, i.e., where phages are used to augment or replace antibiotics; so too adsorption rates are highly important for predicting the potential for phage-mediated biological control of environmental bacteria. Particularly emphasized here, however, are numerous complications on phage adsorption rates beyond as dictated by the ideals of standard adsorption theory. These include movements other than due to diffusion, various hindrances to diffusive movement, and the influence of assorted heterogeneities. Considered chiefly are the biological consequences of these various phenomena rather than their mathematical underpinnings.

Schlesinger Nailed It! Assessing a Key Primary Pharmacodynamic Property of Phages for Phage Therapy: Virion Encounter Rates with Motionless Bacterial Targets

“…If we define k as the likelihood of adsorption given, as noted, the presence of one phage and one cell suspended in 1 mL (i.e., per mL) over one min of time (i.e., per min), then instead we might expect units of mL −1 min −1 , which also can be units used for collision kernels more generally [22]: "number of collisions per unit volume and time". That in fact is how k is sometimes expressed [15], including by this author [12]. Thus, while unit analysis provides us with at least an approximation of the expected units of k as based on R 1 , are those units really the expected units of k, as the phage adsorption-rate constant?…”

“…For phages as antibacterial agents, particularly given phageparticle one-hit killing kinetics [8], pharmacodynamic processes can be distinguished into phages first adsorbing and then their killing resultingly phage-infected bacteria. The rate that bacteria become adsorbed is, in turn, a function of a combination of phage concentrations and what is known as the phage adsorption rate constant [9][10][11][12].…”

Translating phage therapy into the clinic: Recent accomplishments but continuing challenges

“…These are, respectively, some but less than additive increases in the elimination of targeted bacteria relative to each agent acting alone (facilitative), each agent impacting bacteria independently of the other’s actions (additive), and greater than additive bacteria killing (synergism). Synergistic interactions between phages and antibiotics, especially at subinhibitory antibiotic concentrations, can also result in what is described as a phage-antibiotic synergy (PAS) [ 32 , 147 , 179 , 182 , 183 ]. With PAS, the presence of such low antibiotic doses actually enhances certain aspects of phage infection, contrasting the noted potential for higher, inhibitory doses of antibiotics to antagonistically interfere with phage infections.…”

Automating Predictive Phage Therapy Pharmacology

“…If we are considering just a single bacterium, then the average number of adsorptions expected (A c , with the "c" standing for "cell") can be found simply by setting N, the bacterial concentration, to 1 (again keeping in mind that this is all considered as occurring within 1 mL; see Appendix A of [15] for additional detail):…”