Regime Shifts in a Phage-Bacterium Ecosystem and Strategies for Its Control

mSystems. 2019 Nov 5;4(6):e00470-19. doi: 10.1128/mSystems.00470-19.

Abstract

The competition between bacteria often involves both nutrients and phage predators and may give rise to abrupt regime shifts between the alternative stable states characterized by different species compositions. While such transitions have been previously studied in the context of competition for nutrients, the case of phage-induced bistability between competing bacterial species has not been considered yet. Here we demonstrate a possibility of regime shifts in well-mixed phage-bacterium ecosystems. In one of the bistable states, the fast-growing bacteria competitively exclude the slow-growing ones by depleting their common nutrient. Conversely, in the second state, the slow-growing bacteria with a large burst size generate such a large phage population that the other species cannot survive. This type of bistability can be realized as the competition between a strain of bacteria protected from phage by abortive infection and another strain with partial resistance to phage. It is often desirable to reliably control the state of microbial ecosystems, yet bistability significantly complicates this task. We discuss successes and limitations of one control strategy in which one adds short pulses to populations of individual species. Our study proposes a new type of phage therapy, where introduction of the phage is supplemented by the addition of a partially resistant host bacteria.IMPORTANCE Phage-microbe communities play an important role in human health as well as natural and industrial environments. Here we show that these communities can assume several alternative species compositions separated by abrupt regime shifts. Our model predicts these regime shifts in the competition between bacterial strains protected by two different phage defense mechanisms: abortive infection/CRISPR and partial resistance. The history dependence caused by regime shifts greatly complicates the task of manipulation and control of a community. We propose and study a successful control strategy via short population pulses aimed at inducing the desired regime shifts. In particular, we predict that a fast-growing pathogen could be eliminated by a combination of its phage and a slower-growing susceptible host.

Keywords: bacteriophage therapy; bacteriophages; computer modeling; microbial communities; microbial ecology.