Amjad Khan and Lindi Wahl, Applied Math, Western University
Phages are natural predators of bacteria and can be highly effective at killing their bacterial hosts. The use of phages as an alternative of antibiotics is called phage therapy. Bacteria have evolved various defense strategies, ranging from genetic resistance to structural resistance, to deal with both antibiotics and phages. A biofilm is an aggregate of bacteria enclosed in a matrix that is composed of extracellular polymeric substances. It has been shown that biofilm bacteria may be 1000 times more resistant to antibiotic than their planktonic (free-living) counterparts [1]. Phage therapy has been used to control biofilms, but even though phages can inflict substantial damage to these colonies, their action alone is not enough to completely eradicate antibiotic resistant biofilms [2].
Recent experimental studies have examined the effect of combining phage and antibiotic therapy. It was found that using phage therapy first, followed by antibiotics, maximized the killing of bacteria in an established biofilm [3]. We have developed a mathematical model to explore the effect of these therapeutic strategies, i.e., using phages first, followed by antibiotics or vice versa. Preliminary results predict that neither of these strategies can lead to the complete elimination of biofilm. We also suggest a novel therapeutic strategy, which may be effective against antibiotic resistant biofilm colonies.

References
[1] Costerton JW, Stewart PS, Greenberg EP (1999). Bacterial biofilms: a common cause of persistent infections. Science; 284:318–322.
[2] Abedon, S. T. (2015). Ecology of Anti-Biofilm Agents II: Bacteriophage Exploitation and Biocontrol of Biofilm Bacteria. Pharmaceuticals, 8(3), 559–589. http://doi.org/10.3390/ph8030559
[3] Chaudhry WN, Concepción-Acevedo J, Park T, Andleeb S, Bull JJ, Levin BR (2017) Synergy and Order Effects of Antibiotics and Phages in Killing Pseudomonas aeruginosa Biofilms. PLoS ONE 12(1): e0168615. https://doi.org/10.1371/journal.pone.0168615