Leveraging mathematical modeling framework to guide regimen strategy for phage therapy
Fig 1
In vitro data and schematic of each ODE model.
(A) P. aeruginosa PAO1 growth without the addition of phage. (B) P. aeruginosa PAO1 growth after single phage treatment with either phage LUZ19, PYO2, or E215, and after simultaneous double-phage cocktail treatment with a pair of phages from LUZ19, PYO2, and E215. (C) P. aeruginosa PAO1 bacteriophage insensitive mutants (BIM) growth. (D) Schematic of a single phage interaction model. Bacteria (B) replicate at the rate (rn). In the presence of phages (P) that decay at rate (p), sensitive bacteria either mutate (a) into phage resistant single-mutant bacteria (BR) or are bound to and infected by phage (b). Infected bacteria are subsequently moved to the infected class (BI). New phages are released when the infected bacteria cell is lysed (hs). (E) Schematic of a two-phage interaction model with and without collateral phage resistance. In the presence of phages (P1 and P2), bacteria (B) mutate to either receptor-specific single-mutant bacteria (,
) which a phage using an alternate receptor (Pn) can still adsorb to, or become double-mutant bacteria (
) resistant to both receptors. Adsorbed bacteria are subsequently moved to the infected class,
). If the two phages use the same receptor, collateral resistance occurs and the double-mutant is no different than the single mutant, that is BR = BR12 and no additional mutational outcomes emerge and BR1 and BR2 are omitted.