Phenotypic heterogeneity of microbial populations under nutrient limitation

Gasperotti, Ana Florencia; Brameyer, Sophie; Fabiani, Florian; Jung, Kirsten

doi:10.1016/j.copbio.2019.09.016

Cited by 20 publications

(18 citation statements)

References 72 publications

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“…In addition to this delay, we also observed that the ComX defective mutant induced spoIIQ more synchronously than the wild type, which shows prominent heterogeneity in the expression of this marker gene. Phenotypic heterogeneity arises from several different intrinsic and extrinsic factors [78]. Sporulation in B. subtilis is subject to phenotypic heterogeneity due to the noise in the expression of transcriptional regulators, the phosphate transfer in the phosphorylation regulation cascades, and positive and negative feedback loop mechanisms [79].…”

Section: Discussionmentioning

confidence: 99%

The ComX Quorum Sensing Peptide of Bacillus subtilis Affects Biofilm Formation Negatively and Sporulation Positively

et al. 2020

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Quorum sensing (QS) is often required for the formation of bacterial biofilms and is a popular target of biofilm control strategies. Previous studies implicate the ComQXPA quorum sensing system of Bacillus subtilis as a promoter of biofilm formation. Here, we report that ComX signaling peptide deficient mutants form thicker and more robust pellicle biofilms that contain chains of cells. We confirm that ComX positively affects the transcriptional activity of the PepsA promoter, which controls the synthesis of the major matrix polysaccharide. In contrast, ComX negatively controls the PtapA promoter, which drives the production of TasA, a fibrous matrix protein. Overall, the biomass of the mutant biofilm lacking ComX accumulates more monosaccharide and protein content than the wild type. We conclude that this QS phenotype might be due to extended investment into growth rather than spore development. Consistent with this, the ComX deficient mutant shows a delayed activation of the pre-spore specific promoter, PspoIIQ, and a delayed, more synchronous commitment to sporulation. We conclude that ComX mediated early commitment to sporulation of the wild type slows down biofilm formation and modulates the coexistence of multiple biological states during the early stages of biofilm development.

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Section: Discussionmentioning

confidence: 99%

The ComX Quorum Sensing Peptide of Bacillus subtilis Affects Biofilm Formation Negatively and Sporulation Positively

et al. 2020

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“…It is quite possible that the observations made here are applicable to many other stress response systems. However particular interest in the nitrogen starvation response arises from the desire to engineer higher bulk levels of nitrogen fixation ( Gasperotti et al, 2020 ). In this context the significant heterogeneity observed here may impose particular limitations on industrial scale use of diazotrophs ( Delvigne et al, 2014 ), as well as confound the efficient use of clonal populations of diazotrophs in the rhizosphere unless engineered to avoid variance.…”

Section: Discussionmentioning

confidence: 99%

Molecular origins of transcriptional heterogeneity in diazotrophicK. oxytoca

Bashir

Brackston

et al. 2020

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Phenotypic heterogeneity in clonal bacterial batch cultures is an important adaptive 10 strategy to changing environments, including in diazotrophs with the unique capacity to convert 11 di-nitrogen into bio-available ammonium. In diazotrophic Klebsiella oxytoca we simultaneously 12 measured mRNA levels of key regulatory (glnK-amtB, nifLA) and structural (nifHDK) operons required 13 for establishing nitrogen fixation, using dual molecule, single cell RNA-FISH. Through stochastic 14 transcription models and mutual information analysis we revealed likely molecular origins for 15 heterogeneity in nitrogenase expression. In wildtype and regulatory variant strains we inferred 16 contributions from intrinsic and extrinsic noise, finding that nifHDK transcription is inherently 17 bursty, but that noise propagation through signalling is also significant. The regulatory gene glnK 18 had the highest discernible effect on nifHDK variance, while noise from factors outside of the 19 regulatory pathway were negligible. Results provide evidence that heterogeneity is a fundamental 20 property of this regulatory system, indicating potential constraints for engineering homogeneous 21 nitrogenase expression. 22 30 Phenotypic heterogeneity may be particularly relevant in costly stress response systems, of 31 which the response to nitrogen starvation is a key example (Schreiber et al., 2016). In organisms 32 such as Klebsiella oxytoca, nitrogen starvation triggers a transition to diazotrophic behaviour in 33 which bacterial cells use atmospheric di-nitrogen as their nitrogen source for growth (Dixon and 34 Kahn, 2004). While this transition, and the associated transcriptional programme, is essential 35 for continued growth under conditions deplete of fixed nitrogen, it is also very costly since the 36 resultant ATP consuming nitrogenase enzyme may ultimately constitute up to 20 % of the proteome 37 (Dixon and Kahn, 2004). As such, if fixed nitrogen sources soon become available again, it is likely 38 advantageous to have not fully undergone the diazotrophic transition. Activation of the nitrogen 39 stress response is potentially somewhat of a gamble in which the payoff depends strongly on future 40 1 of 15conditions. Such a scenario may therefore indicate a requirement for bet-hedging strategies in 41 which heterogeneity proves advantageous at the population level (van Boxtel et al., 2017). 42 Regardless of whether there are advantages to heterogeneity, it is also important to establish 43 the underlying mechanistic causes, especially if there is an aim to ultimately modify cell behaviour. 44 Studies at single-cell resolution are crucial to this, enabling the full distribution of expression levels 45 to be obtained over a population of cells. Such data not only provides qualitative insight into the 46 variability between cells, but can also enable the inference of the underlying dynamical processes 47 and predicts the probability distribution of mRNA copy numbers (Ko, 1991; Peccoud and Ycart, 1995; 87 ., 2006;...

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“…Such non-genetic phenotypic cell-to-cell variation may underlie the observed response to perturbations (Figure 3). Phenotypic heterogeneity may occur owing to intrinsic factors (e.g., individual physiological state, stochastic gene expression/noise, and cell-cycle phases) and/or heterogeneous extrinsic factors (e.g., chemical mixing gradients and variation in cell density) [37]. Phenotypic heterogeneity may thus be reversible, whereas the emergence of genetic heterogeneity represents intrinsic one-way Trends Trends in in Biotechnology Biotechnology Figure 3.…”

Section: Population Dynamics At Single-cell Resolution Provides Insights Into Robustness Mechanismsmentioning

confidence: 99%