On the Ecological Significance of Phenotypic Heterogeneity in Microbial Populations Undergoing Starvation

To persist in variable environments populations of microorganisms have to survive periods of starvation and be able to restart cell division in nutrient-rich conditions. Typically, starvation signals initiate a transition to a quiescent state in a fraction of individual cells, while the rest of the cells remain non-quiescent. It is widely believed that, while quiescent cells (Q) help the population to survive long starvation, the non-quiescent cells (NQ) are a side effect of imperfect transition. We analysed regrowth of starved monocultures of Q and NQ cells compared to mixed, heterogeneous cultures in simple and complex starvation environments. Our experiments, as well as mathematical modelling, demonstrate that Q monocultures benefit from better survival during long starvation, and from a shorter lag phase after resupply of rich medium. However, when the starvation period is very short, the NQ monocultures outperform Q and mixed cultures, due to their short lag phase. In addition, only NQ monocultures benefit from complex starvation environments, where nutrient recycling is possible. Our study suggests that phenotypic heterogeneity in starved populations could be a form of bet hedging, which is adaptive when environmental determinants, such as the length of the starvation period, the length of the regrowth phase, and the complexity of the starvation environment vary over time.

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Ecological feedback in quorum-sensing microbial populations can induce heterogeneous production of autoinducers

eLife ◽

10.7554/elife.25773 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 12

Author(s):

Matthias Bauer ◽

Johannes Knebel ◽

Matthias Lechner ◽

Peter Pickl ◽

Erwin Frey

Keyword(s):

Gene Expression ◽

Quorum Sensing ◽

Promoter Activity ◽

Phenotypic Heterogeneity ◽

Microbial Populations ◽

Alternative Mechanism ◽

Stochastic Gene Expression ◽

Regulatory Circuits ◽

Gene Regulatory ◽

Gene Regulatory Circuits

Autoinducers are small signaling molecules that mediate intercellular communication in microbial populations and trigger coordinated gene expression via ‘quorum sensing’. Elucidating the mechanisms that control autoinducer production is, thus, pertinent to understanding collective microbial behavior, such as virulence and bioluminescence. Recent experiments have shown a heterogeneous promoter activity of autoinducer synthase genes, suggesting that some of the isogenic cells in a population might produce autoinducers, whereas others might not. However, the mechanism underlying this phenotypic heterogeneity in quorum-sensing microbial populations has remained elusive. In our theoretical model, cells synthesize and secrete autoinducers into the environment, up-regulate their production in this self-shaped environment, and non-producers replicate faster than producers. We show that the coupling between ecological and population dynamics through quorum sensing can induce phenotypic heterogeneity in microbial populations, suggesting an alternative mechanism to stochastic gene expression in bistable gene regulatory circuits.

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THE GLUCOSE UPTAKE KINETICS OF SOME MARINE BACTERIA

Canadian Journal of Microbiology ◽

10.1139/m66-134 ◽

1966 ◽

Vol 12 (5) ◽

pp. 995-1003 ◽

Cited By ~ 14

Author(s):

R. D. Hamilton ◽

K. M. Morgan ◽

J. D. H. Strickland

Keyword(s):

Glucose Uptake ◽

Marine Bacteria ◽

Uptake Kinetics ◽

Microbial Populations ◽

Ecological Significance ◽

Factors Affecting ◽

Low Concentrations ◽

Pure Cultures ◽

Low Levels ◽

Kinetics Of

The kinetics of glucose uptake by marine microbial populations have been investigated. Pure cultures were used in an attempt to define the conditions affecting uptake kinetics. The use of routine marine microbiological media did not isolate microorganisms capable of responding to the substrate levels that one might expect to find in the ocean, but a chemostat approach was successful in the isolation of such forms. Some factors affecting the uptake of glucose at very low levels were investigated. The kinetic approach with pure cultures has possible application as a bioassay method for substrates in low concentrations in seawater. The ecological significance of the investigation is discussed.

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Crosstalk between guanosine nucleotides regulates cellular heterogeneity in protein synthesis during nutrient limitation

10.1101/2021.11.22.469502 ◽

2021 ◽

Author(s):

Simon Diez ◽

Molly Hydorn ◽

Abigail Whalen ◽

Jonathan Dworkin

Keyword(s):

Protein Synthesis ◽

Bacillus Subtilis ◽

Nutrient Limitation ◽

Dynamic Environments ◽

Phenotypic Heterogeneity ◽

Cellular Heterogeneity ◽

Microbial Populations ◽

Low Protein ◽

Synthesis Activity

Phenotypic heterogeneity of microbial populations can facilitate survival in dynamic environments by generating sub-populations of cells that may have differential fitness in a future environment. Bacillus subtilis cultures experiencing nutrient limitation contain distinct sub-populations of cells exhibiting either comparatively high or low protein synthesis activity. This heterogeneity requires the production of phosphorylated guanosine nucleotides (pp)ppGpp by three synthases: SasA, SasB, and RelA. Here we show that these enzymes differentially affect this bimodality: RelA and SasB are necessary to generate the sub-population of cells exhibiting low protein synthesis whereas SasA is necessary to generate cells exhibiting comparatively higher protein synthesis. The RelA product (pppGpp) allosterically activates SasB and we find, in contrast, that the SasA product (pGpp) competitively inhibits this activation. Finally, we provide in vivo evidence that this antagonistic interaction mediates the observed heterogeneity in protein synthesis. This work therefore identifies the mechanism underlying phenotypic heterogeneity in the central physiological process of protein synthesis.

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Phenotypic heterogeneity of microbial populations under nutrient limitation

Current Opinion in Biotechnology ◽

10.1016/j.copbio.2019.09.016 ◽

2020 ◽

Vol 62 ◽

pp. 160-167 ◽

Cited By ~ 4

Author(s):

Ana Gasperotti ◽

Sophie Brameyer ◽

Florian Fabiani ◽

Kirsten Jung

Keyword(s):

Nutrient Limitation ◽

Phenotypic Heterogeneity ◽

Microbial Populations

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Phenotypic heterogeneity implements a game theoretic mixed strategy in a clonal microbial population

10.1101/011049 ◽

2014 ◽

Cited By ~ 3

Author(s):

David Healey ◽

Jeff Gore

Keyword(s):

Experimental Evidence ◽

Evolutionary Game ◽

Phenotypic Heterogeneity ◽

Microbial Populations ◽

Bet Hedging ◽

Hedging Strategy ◽

Unpredictable Environments ◽

Game Theoretic ◽

Pure Strategies ◽

Genetic Mutants

Genetically identical cells in microbial populations often exhibit a remarkable degree of phenotypic heterogeneity even in homogenous environments. While such heterogeneity is often thought to be a bet-hedging strategy against unpredictable environments, evolutionary game theory also predicts phenotypic heterogeneity as a stable response to evolutionary "hawk-dove" games, in which rare strategies are favored over common ones. Here we provide experimental evidence for this game theoretic explanation in the context of the well-studied yeast GAL network. In an environment containing the two sugars glucose and galactose, the yeast GAL network displays stochastic bimodal activation. We show that genetic mutants playing the "pure" strategies of GAL-ON or GAL-OFF can each invade the opposite strategy when rare, indicating a hawk-dove game between the two. Consistent with the Nash equilibrium of an evolutionary game, the stable mix of pure strategists does not necessarily maximize the growth of the overall population. We also find that the wild type GAL network can invade populations of both pure strategists while remaining uninvasible by either. Taken together, our results provide experimental evidence that evolutionary hawk-dove games between identical cells can explain the phenotypic heterogeneity found in clonal microbial populations.

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