R-063. Quorum-Controlled Lantibiotics Enforce Cooperative Behavior within Bacillus subtilis Populations

D. N. Adamson1, D. M. Wolf2, A. Arkin1,2;
1Univ. of California, Berkeley, CA, 2Lawrence Berkeley Natl. Lab., Berkeley, CA.

Antibiotic warfare and quorum sensing are general themes in microbial ecology and evolution. Antibiotic synthesis is generally used in defense or predation while quorum sensing has been conjectured to coordinate population response. Interestingly, Bacillus subtilis implements a survival strategy which couples these phenomena; synthesis of the lantibiotic subtilin is under quorum control. The subtilin regulatory circuitry is intriguing in that it links production of the antibiotic warhead (subtilin), with expression of the resistance gene (SpaI). The two-component system (SpaRK) that enables cells to sense a quorum and thus produce both the antibiotic and its immunity factor is only activated when the cell enters stationary phase. Thus once the subpopulation of cells first in stationary phase reach the density required to initiate subtilin production, any kin cells that remain in exponential phase will presumably die. A priori, it seems a poor evolutionary strategy to produce antibiotics that will kill off a portion of ones’ own population, especially when stochastic effects could cause even clonal populations to switch into stationary growth phase at different times. Here, we apply an evolutionary game theoretic analysis to identify the circumstances in which this strategy enhances fitness. Results indicate that in harsh environments, while the optimal overall strategy is for cells in high-density populations to cooperate to conserve resources when entering a possibly lengthy period of starvation, the incentive to individual cells is to delay entry into stationary phase and rapidly consume remaining resources. But such ‘cheaters’ result in faster starvation of the population as a whole. We show that this Prisoner’s Dilemma dynamic, where cooperation is optimal but not evolutionary stable, is disrupted by the subtilin circuitry because it selects against exponential phase ‘cheaters’. We hypothesize that quorum-controlled antibiotic systems solve the problem of how to enforce cooperative resource conservation, a surprising result considering that antibiotics are generally thought of as weapons for use against other species.

290/R. Comparative and Evolutionary Genomics - I

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