Microbial bet-hedging: the power of being different
Introduction
‘You cannot stop the waves, but you can learn to surf’—Jon Kabat-Zinn. When organisms live in an ever-changing environment, the ability to maximize fitness is crucial. But how do microorganisms prepare for unpredictable environmental changes? How do microorganisms ‘surf’?
One way to prepare for an uncertain future is by employing a survival strategy known as ‘bet-hedging’; an organism spreads risks to increase long term fitness in a fluctuating environment. The observation that genetically identical microbes can stochastically develop phenotypes with varying fitness in a homogenous environment enticed microbiologists to adopt this evolutionary theory. It may, however, occur that ‘bet-hedging’ is used to explain any form of microbial phenotypic heterogeneity, despite bet-hedging being strictly defined. The theory of bet-hedging originates from studies on macroorganismal systems and it is challenging to define whether observations in microbes fit that framework. This is due to microbial characteristics like high phenotypic plasticity and mutation rates, and due to environmental characteristics that are hard to quantify. Here, we discuss some recent studies in the context of microbial bet-hedging. Furthermore, we discuss what type of experiments can reveal the existence of bet-hedging strategies in microorganisms.
Section snippets
Definition of ‘bet-hedging’
Bet-hedging is a survival strategy in which an isogenic population minimizes the temporal variance of surviving offspring and so maximizes the geometric mean fitness across various environments (Eqs. (1), (2)). This is achieved by individuals that stochastically develop a phenotype of reduced fitness that may be better adapted to a future environment. This is predicted to be a successful survival strategy in case an environment changes unpredictably with a severe cost for maladaptation in the
Noisy gene expression: a mechanism behind phenotypic heterogeneity
Microbes have the ability to differentiate in response to environmental cues by making use of sensory circuits [4]. However, molecules involved in biochemical reactions depend on chance for encountering the appropriate molecules to interact- or react with [5, 6]. This introduces noise in such circuits and can cause a cellular response without the input of an environmental cue (stochastic phenotype determination) [7, 8]. The impact of noise can be particularly severe in bistable regulatory
Classification of bet-hedging evidence
In order to test whether observed phenotypical heterogeneity convincingly qualifies as a bet-hedging strategy, Simons (2011) proposed categories for evidence [2•]. In order to fall within the highest category VI, evidence for true bet-hedging, studies must demonstrate that (a) the bet-hedging trait increases fitness compared to a non-bet-hedging alternative in a fluctuating environment and (b) show that the phenotype switching rate correlates with environmental fluctuation frequency in order to
Endospore formation in B. subtilis
Sporulation in Bacillus subtilis is a last resort response to starvation. The highly resistant endospore increases survival in harsh conditions at the cost of reduced reproductive offspring [15]. It is a good example of phenotype switching driven by a bistable regulatory network that, besides incorporating environmental information, allows stochastic switching by incorporating noise in regulatory elements [16, 17, 18] (Figure 2). Formation of an endospore is an expensive dead-end strategy;
Bet-hedging in carbon metabolism
Similarly to Bacillus, Dictyostelium discoideum cells diversify their commitment to sporulation; some individuals aggregate and commit to spore formation while others do not [23]. This diversification, however, takes place once nutrients are deprived. This contrasts with stochastic sporulation preceding nutrient limitation as observed in B. subtilis. Stochastic sporulation by Bacillus is a conservative bet-hedging type strategy (‘insurance policy’), while D. discoideum displays responsive
Bet-hedging causing a medical problem: Persisters
Bacteria can survive antibiotic treatment by either developing immunity through mutations or gene acquisition, or developing tolerance [33, 34]. It has been observed that bacteria can stochastically enter a state of dormancy. The reduced cellular activity results in reduced targets for antibiotic activity [35]. These dormant cells, or persister cells, can grow out once antibiotic pressure is relieved, producing fast-growing, antibiotic-sensitive offspring and thus are a major cause of
Discussion
Stochastic spore development in Bacillus, and development of persisters show strong evidence of bet-hedging since a subpopulation with reduced reproductive success stochastically arises before the environment changes [21, 31, 35]. Responsive diversification, on the other hand, causes controversy as reflected in the manuscript by New et al. The authors mention that their observations do not justify the claim of bet-hedging because the phenotypic heterogeneity only manifests itself when maltose
Experimental challenges/future outlook
Future studies on organisms that display a candidate bet-hedging trait should focus on extended cultivation in either predictable or unpredictable fluctuating environments. This should provide quantitative data on surviving offspring over the course of several environmental changes. Challenging cultures with multiple selection pressures can also be very informative: each environment requires a different (set of) sensory proteins for environmental cues, while stochastic development of sub-fit
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest.
Acknowledgements
The authors would like to thank Dr. G. Sander van Doorn and Renske van Raaphorst for critically reviewing the manuscript. AJG is funded by the Dutch Science Organization, NWO (ALW project 433244).
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2022, Biotechnology AdvancesCitation Excerpt :Upon facing environmental changes, single cells of a population stochastically develop different co-existing phenotypes to prepare for future environmental changes they will encounter with a certain probability. This mechanism, referred to as Bet-hedging, acts as a protection against stress when facing repeated changes e.g. nutrient availability or heat stress (Grimbergen et al., 2015; Jõers and Tenson, 2016; Levy et al., 2012; Solopova et al., 2014; Takahashi et al., 2015). For further details on the classification of population heterogeneity and its influences, the reader is referred to several review articles covering this topic (Davis and Isberg, 2016; Delvigne et al., 2014; Heins and Weuster-Botz, 2018).
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2022, Trends in MicrobiologyCitation Excerpt :The benefits of phenotypic variation are usually characterized as bet-hedging [37] or division of labor [38] survival strategies (Figure 2). Bet-hedging allows a clonal bacterial population to optimally adapt to consecutive, rapid and frequent fluctuations in environmental conditions without the need to respond to external signals [39]. Division of labor takes place when individuals in a clonal population interact with each other and concomitantly express distinct, often complementary, traits [40].