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Slower growth of Escherichia coli leads to longer survival in carbon starvation due to a decrease in the maintenance rate.

ABSTRACT: Fitness of bacteria is determined both by how fast cells grow when nutrients are abundant and by how well they survive when conditions worsen. Here, we study how prior growth conditions affect the death rate of Escherichia coli during carbon starvation. We control the growth rate prior to starvation either via the carbon source or via a carbon-limited chemostat. We find a consistent dependence where death rate depends on the prior growth conditions only via the growth rate, with slower growth leading to exponentially slower death. Breaking down the observed death rate into two factors, maintenance rate and recycling yield, reveals that slower growing cells display a decreased maintenance rate per cell volume during starvation, thereby decreasing their death rate. In contrast, the ability to scavenge nutrients from carcasses of dead cells (recycling yield) remains constant. Our results suggest a physiological trade-off between rapid proliferation and long survival. We explore the implications of this trade-off within a mathematical model, which can rationalize the observation that bacteria outside of lab environments are not optimized for fast growth.

SUBMITTER: Biselli E

PROVIDER: S-EPMC7273699 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Growth substrates, aerobic/anaerobic conditions, specific growth rate (?) etc. strongly influence Escherichia coli cell physiology in terms of cell size, biomass composition, gene and protein expression. To understand the regulation behind these different phenotype properties, it is useful to know carbon flux patterns in the metabolic network which are generally calculated by metabolic flux analysis (MFA). However, rarely is biomass composition determined and carbon balance carefully measured in the same experiments which could possibly lead to distorted MFA results and questionable conclusions. Therefore, we carried out both detailed carbon balance and biomass composition analysis in the same experiments for more accurate quantitative analysis of metabolism and MFA. RESULTS: We applied advanced continuous cultivation methods (A-stat and D-stat) to continuously monitor E. coli K-12 MG1655 flux and energy metabolism dynamic responses to change of ? and glucose-acetate co-utilisation. Surprisingly, a 36% reduction of ATP spilling was detected with increasing ? and carbon wasting to non-CO2 by-products under constant biomass yield. The apparent discrepancy between constant biomass yield and decline of ATP spilling could be explained by the rise of carbon wasting from 3 to 11% in the carbon balance which was revealed by the discovered novel excretion profile of E. coli pyrimidine pathway intermediates carbamoyl-phosphate, dihydroorotate and orotate. We found that carbon wasting patterns are dependent not only on ?, but also on glucose-acetate co-utilisation capability. Accumulation of these compounds was coupled to the two-phase acetate accumulation profile. Acetate overflow was observed in parallel with the reduction of TCA cycle and glycolysis fluxes, and induction of pentose phosphate pathway. CONCLUSIONS: It can be concluded that acetate metabolism is one of the major regulating factors of central carbon metabolism. More importantly, our model calculations with actual biomass composition and detailed carbon balance analysis in steady state conditions with -omics data comparison demonstrate the importance of a comprehensive systems biology approach for more advanced understanding of metabolism and carbon re-routing mechanisms potentially leading to more successful metabolic engineering.

Project description:ObjectivesSlowed speaking rate was examined for its effects on speech intelligibility, its interaction with the benefit of contextual cues, and the impact of these factors on listening effort in adults with cochlear implants.DesignParticipants (n = 21 cochlear implant users) heard high- and low-context sentences that were played at the original speaking rate, as well as a slowed (1.4× duration) speaking rate, using uniform pitch-synchronous time warping. In addition to intelligibility measures, changes in pupil dilation were measured as a time-varying index of processing load or listening effort. Slope of pupil size recovery to baseline after the sentence was used as an index of resolution of perceptual ambiguity.ResultsSpeech intelligibility was better for high-context compared to low-context sentences and slightly better for slower compared to original-rate speech. Speech rate did not affect magnitude and latency of peak pupil dilation relative to sentence offset. However, baseline pupil size recovered more substantially for slower-rate sentences, suggesting easier processing in the moment after the sentence was over. The effect of slowing speech rate was comparable to changing a sentence from low context to high context. The effect of context on pupil dilation was not observed until after the sentence was over, and one of two analyses suggested that context had greater beneficial effects on listening effort when the speaking rate was slower. These patterns maintained even at perfect sentence intelligibility, suggesting that correct speech repetition does not guarantee efficient or effortless processing. With slower speaking rates, there was less variability in pupil dilation slopes following the sentence, implying mitigation of some of the difficulties shown by individual listeners who would otherwise demonstrate prolonged effort after a sentence is heard.ConclusionsSlowed speaking rate provides release from listening effort when hearing an utterance, particularly relieving effort that would have lingered after a sentence is over. Context arguably provides even more release from listening effort when speaking rate is slower. The pattern of prolonged pupil dilation for faster speech is consistent with increased need to mentally correct errors, although that exact interpretation cannot be verified with intelligibility data alone or with pupil data alone. A pattern of needing to dwell on a sentence to disambiguate misperceptions likely contributes to difficulty in running conversation where there are few opportunities to pause and resolve recently heard utterances.

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Slower growth of Escherichia coli leads to longer survival in carbon starvation due to a decrease in the maintenance rate.

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