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Open Access Publications from the University of California

Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2018)

Growth and reproduction are essential requirements of living systems. Previous studies of bacterial physiology focused largely on bacteria growing exponentially in fixed environments. But such growth conditions are exception rather than the norm in nature. Bacteria in the wild must cope with environments that vary temporally and spatially. To gain better understanding of bacterial physiology, I studied growth of E. coli population in 1) dynamic nutrient environment and 2) spatially extended environment.

Rapid adaptation is a crucial determinant of bacterial fitness under changing environments. We studied adaptation of E. coli culture to abrupt change of nutrient from preferred sugars (e.g., glucose) to a metabolic waste product (e.g., acetate) that is excreted during the growth on preferred substrates. In such transitions, E. coli suffers long, multi-hour periods of growth arrest before resuming growth. By characterizing the period of growth arrest (lag time) for many pairs of carbon sources, we discovered that cells growing fast before the shift exhibit longer lag time, resulting in a remarkable trade- off relationship between fast growth and adaptability. We establish that this tradeoff results from switching the direction of central carbon metabolism from glycolysis to gluconeogenesis. The existence of tradeoff limits fitness benefit gained from fast growth and provides a criterion for selecting growth rates based on the expected abundances of substrates in the environment.

In spatially open habitats, effective colonization provides a selective advantage for bacterial populations. We next studied the growth of E. coli population that expands by chemotaxis in nutrient-replete soft-agar plates. We show the speed of population expansion, as exemplified by the propagation of chemotactic rings, increases steadily with improved growth conditions. The expansion process is shown to couple intricately with colonization, with the propagating cells leave behind a trail of offspring that slowly proliferate over time. We also show costly expression of motility apparatus is necessary to maintain the fraction of motile cells and support faster population expansion. The results provide a link from gene expression through cellular motility all the way to population dynamics, elucidating a foresighted strategy bacteria use to colonize virgin territories well before local nutrient supply runs out.

    Cover page: Growth of bacterial population in dynamic and spatially extended environments
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2022)
    To swim and navigate, motile bacteria synthesize a complex motility machinery involving flagella, motors, and a sensory system. A myriad of studies has elucidated the molecular processes involved, but less is known about the coordination of motility expression with cellular physiology: In Escherichia coli, motility genes are strongly up-regulated in nutrient-poor conditions compared to nutrient-replete conditions; yet a quantitative link to cellular motility has not been developed. Here, we systematically investigated gene expression, swimming behavior, cell growth, and available proteomics data across a broad spectrum of exponential growth conditions. Our results suggest that cells up-regulate the expression of motility genes at slow growth to compensate for reduction in cell size, such that the number of flagella per cell is maintained across conditions. The observed four or five flagella per cell is the minimum number needed to keep the majority of cells motile. This simple regulatory objective allows E. coli cells to remain motile across a broad range of growth conditions, while keeping the biosynthetic and energetic demands to establish and drive the motility machinery at the minimum needed. Given the strong reduction in flagella synthesis resulting from cell size increases at fast growth, our findings also provide a different physiological perspective on bacterial cell size control: A larger cell size at fast growth is an efficient strategy to increase the allocation of cellular resources to the synthesis of those proteins required for biomass synthesis and growth, while maintaining processes such as motility that are only needed on a per-cell basis.
      Cover page: Coordination of gene expression with cell size enables Escherichia coli to efficiently maintain motility across conditions
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2019)
      Bacterial chemotaxis, the directed movement of cells along gradients of chemoattractants, is among the best-characterized subjects in molecular biology1-10, but much less is known about its physiological roles11. It is commonly seen as a starvation response when nutrients run out, or as an escape response from harmful situations12-16. Here we identify an alternative role of chemotaxis by systematically examining the spatiotemporal dynamics of Escherichia coli in soft agar12,17,18. Chemotaxis in nutrient-replete conditions promotes the expansion of bacterial populations into unoccupied territories well before nutrients run out in the current environment. Low levels of chemoattractants act as aroma-like cues in this process, establishing the direction and enhancing the speed of population movement along the self-generated attractant gradients. This process of navigated range expansion spreads faster and yields larger population gains than unguided expansion following the canonical Fisher-Kolmogorov dynamics19,20 and is therefore a general strategy to promote population growth in spatially extended, nutrient-replete environments.
        Cover page: Chemotaxis as a navigation strategy to boost range expansion
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2020)
        The rate of cell growth is crucial for bacterial fitness and drives the allocation of bacterial resources, affecting, for example, the expression levels of proteins dedicated to metabolism and biosynthesis1,2. It is unclear, however, what ultimately determines growth rates in different environmental conditions. Moreover, increasing evidence suggests that other objectives are also important3-7, such as the rate of physiological adaptation to changing environments8,9. A common challenge for cells is that these objectives cannot be independently optimized, and maximizing one often reduces another. Many such trade-offs have indeed been hypothesized on the basis of qualitative correlative studies8-11. Here we report a trade-off between steady-state growth rate and physiological adaptability in Escherichia coli, observed when a growing culture is abruptly shifted from a preferred carbon source such as glucose to fermentation products such as acetate. These metabolic transitions, common for enteric bacteria, are often accompanied by multi-hour lags before growth resumes. Metabolomic analysis reveals that long lags result from the depletion of key metabolites that follows the sudden reversal in the central carbon flux owing to the imposed nutrient shifts. A model of sequential flux limitation not only explains the observed trade-off between growth and adaptability, but also allows quantitative predictions regarding the universal occurrence of such tradeoffs, based on the opposing enzyme requirements of glycolysis versus gluconeogenesis. We validate these predictions experimentally for many different nutrient shifts in E. coli, as well as for other respiro-fermentative microorganisms, including Bacillus subtilis and Saccharomyces cerevisiae.
          Cover page: A universal trade-off between growth and lag in fluctuating environments
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