TY - JOUR T1 - Chance is an important element in phagolysosomal acidification that favors the macrophage JF - bioRxiv DO - 10.1101/470617 SP - 470617 AU - Quigly Dragotakes AU - Kaitlin Stouffer AU - Man Shun Fu AU - Carlos M. De Leon-Rodriguez AU - Joudeh B. Freij AU - Aviv Bergman AU - Arturo Casadevall Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/11/15/470617.abstract N2 - Phagosome acidification is a critical mechanism of defense in phagocytic cells, which inhibits microbes by producing a less hospitable pH that also activates microbicidal mechanisms. We analyzed the dynamic distribution of phagolysosome pH measurements after bone marrow derived macrophages had ingested live Cryptococcus neoformans or C. gattii cells, dead C. neoformans cells, or inert beads at various time intervals. Phagosomes acidified for each type of ingested particle, producing a range of pH values that approximated normal distributions, yet the degree to which they differed from normality depended on the particle type. Irrespective of the particle ingested, we noted wide variation in the phagolysosomal pH measured. Analysis of the increment of pH reduction revealed no forbidden ordinal pH intervals for each type of particle indicative of chaotic signatures; consistent with the notion that the phagosomal acidification process is a result of a stochastic dynamical system. The stochastic nature of phagosomal acidification is consistent with the fact that final vacuolar pH is the result of numerous variables that contribute to the final outcome, which was also reflected in a stochastic initiation of intracellular cell budding. Hence, “chance” plays an important role in the process of phagosomal acidification which, in turn, introduces unpredictability to the outcome of the macrophage-microbe struggle in individual phagosomes thus creating a fundamental uncertainty in the fate of host-microbe interactions. Chance provides macrophages with an adaptive bet hedging strategy that can increase the likelihood that phagolysosomal pH inhibits ingested microbes while reducing the emergence of acid resistance. ER -