Phenotypic Diversity as a Mechanism to Exit Cellular Dormancy

Abstract

Microorganisms can facilitate their survival in stressful environments by entering a state of metabolic inactivity or dormancy [1]. However, this state impairs the function of the very sensory systems necessary to detect favorable growth conditions. Thus, how can a metabolically quiescent cell accurately monitor environmental conditions in order to best decide when to exit dormancy? One strategy employed by microbes to deal with changing environments is the generation of phenotypes that may be less well adapted to a current condition but might confer an advantage in the future [2, 3]. This bet-hedging depends on phenotypic diversity in the population [4], which itself can derive from naturally occurring stochastic differences in gene expression [5, 6]. In the case of metabolic dormancy, a bet-hedging strategy that has been proposed is the "scout model" where cells comprising a fraction of the dormant population reinitiate growth stochastically, independent of environmental cues [7, 8]. Here, we provide experimental evidence that such a mechanism exists in dormant spores produced by the ubiquitous soil bacterium Bacillus subtilis. We observe that these spores reinitiate growth at a low but measureable frequency even in the absence of an inducing signal. This phenomenon is the result of phenotypic variation in the propensity of individual spores to reinitiate growth spontaneously. Since this bet-hedging mechanism produces individuals that will either grow under favorable conditions or die under unfavorable conditions, a population can properly respond to environmental changes despite the impaired sensory ability of individual cells.