The quantitative and condition-dependent Escherichia coli proteome

Schmidt, Alexander; Kochanowski, Karl; Vedelaar, Silke R.; Ahrné, Erik; Volkmer, Benjamin; Callipo, Luciano; Knoops, Kèvin; Bauer, Manuel; Aebersold, Ruedi; Heinemann, Matthias

doi:10.1038/nbt.3418

Cited by 708 publications

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“…http://dx.doi.org/10.1101/113183 doi: bioRxiv preprint first posted online Mar. 2, 2017; 2 the expense of catabolic, motility and biosynthetic proteins [1,10,28]. Similar changes are observed in cells subject to other modes of growth limitation, like nitrogen starvation or translational inhibition [10].…”

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confidence: 52%

“…In E. coli, for instance, a substantial reshaping of the proteome takes place in carbon-limited growth, with ribosome-affiliated proteins taking up an increasing fraction of the proteome as the bulk growth rate µ increases, at the expense of catabolic, motility and biosynthetic proteins [1,10,28]. Similar changes are observed in cells subject to other modes of growth limitation, like nitrogen starvation or translational inhibition [10].…”

Section: General View Of the Optimal Proteome Allocation Problemmentioning

confidence: 50%

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A yield-cost tradeoff governs Escherichia coli's decision between fermentation and respiration in carbon-limited growth

Mori

Marinari

Martino

2017

Preprint

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Many microbial systems are known to actively reshape their proteomes in response to changes in growth conditions induced e.g. by nutritional stress or antibiotics. Part of the re-allocation accounts for the fact that, as the growth rate is limited by targeting specific metabolic activities, cells simply respond by fine-tuning their proteome to invest more resources into the limiting activity (i.e. by synthesizing more proteins devoted to it). However, this is often accompanied by an overall re-organization of metabolism, aimed at improving the growth yield under limitation by re-wiring resource through different pathways. While both effects impact proteome composition, the latter underlies a more complex systemic response to stress. By focusing on E. coli's 'acetate switch', we use mathematical modeling and a re-analysis of empirical data to show that the transition from a predominantly fermentative to a predominantly respirative metabolism in carbon-limited growth results from the trade-off between maximizing the growth yield and minimizing its costs in terms of required the proteome share. In particular, E. coli's metabolic phenotypes appear to be Pareto-optimal for these objective functions over a broad range of dilutions.The physiology of cell growth can nowadays be experimentally probed in exponentially growing bacteria both at bulk (see e.g. the bacterial growth laws detailed in [1][2][3]) and at single cell resolution [4][5][6][7]. Refining the picture developed since the 1950s [8,9], recent studies have shown that changes in growth conditions are accompanied by a massive re-organization of the cellular proteome, whereby resources are re-distributed among protein classes (e.g. transporters, metabolic enzymes, ribosome-affiliated proteins, etc.) so as to achieve optimal growth performance [10]. This in turn underlies significant modifications in cellular energetics to cope with the increasing metabolic burden of fast growth [11][12][13].E. coli's 'acetate switch' is a major manifestation of the existence of a complex interplay between metabolism and gene expression. Slowly growing E. coli cells tend to operate close to the theoretical limit of maximum biomass yield [14,15]. Fast-growing cells, instead, typically show lower yields, together with the excretion of carbon equivalents such as acetate [13]. One can argue that, in the latter regime, cells optimize enzyme usage, i.e. they minimize the protein costs associated to growth, while at slow growth they try to use nutrients as efficiently as possible [13]. As one crosses over from one regime to the other, E. coli's growth physiology appears to be determined to a significant extent by the trade-off between growth and its biosynthetic costs. Interestingly, a similar overflow scenario appears in other cell types in proliferating regimes (see e.g. the Crabtree effect in yeast [16,17] or the Warburg effect in cancer cells [18][19][20]).Several phenomenological models have tackled the issue of how metabolism and gene expression coordinate to optimize growth in ...

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confidence: 52%

Section: General View Of the Optimal Proteome Allocation Problemmentioning

confidence: 50%

A yield-cost tradeoff governs Escherichia coli's decision between fermentation and respiration in carbon-limited growth

Mori

Marinari

Martino

2017

Preprint

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“…Membrane-bound respiratory complexes constitute a major part of the IM proteome (37). Therefore, their elaboration and function may impose significant stress on the IM.…”

Section: Discussionmentioning

confidence: 99%

A Bacterial Stress Response Regulates Respiratory Protein Complexes To Control Envelope Stress Adaptation

et al. 2017

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The Cpx envelope stress response mediates adaptation to stresses that affect protein folding within the envelope of Gram-negative bacteria. Recent transcriptome analyses revealed that the Cpx response impacts genes that affect multiple cellular functions predominantly associated with the cytoplasmic membrane. In this study, we examined the connection between the Cpx response and the respiratory complexes NADH dehydrogenase I and cytochrome bo 3 in enteropathogenic Escherichia coli. We found that the Cpx response directly represses the transcription of the nuo and cyo operons and that Cpx-mediated repression of these complexes confers adaptation to stresses that compromise envelope integrity. Furthermore, we found that the activity of the aerobic electron transport chain is reduced in E. coli lacking a functional Cpx response despite no change in the transcription of either the nuo or the cyo operon. Finally, we show that expression of NADH dehydrogenase I and cytochrome bo 3 contributes to basal Cpx pathway activity and that overproduction of individual subunits can influence pathway activation. Our results demonstrate that the Cpx response gauges and adjusts the expression, and possibly the function, of inner membrane protein complexes to enable adaptation to envelope stress.IMPORTANCE Bacterial stress responses allow microbes to survive environmental transitions and conditions, such as those encountered during infection and colonization, that would otherwise kill them. Enteric microbes that inhabit or infect the gut are exposed to a plethora of stresses, including changes in pH, nutrient composition, and the presence of other bacteria and toxic compounds. Bacteria detect and adapt to many of these conditions by using envelope stress responses that measure the presence of stressors in the outermost compartment of the bacterium by monitoring its physiology. The Cpx envelope stress response plays a role in antibiotic resistance and host colonization, and we have shown that it regulates many functions at the bacterial inner membrane. In this report, we describe a novel role for the Cpx response in sensing and controlling the expression of large, multiprotein respiratory complexes at the cytoplasmic membrane of Escherichia coli. The significance of our research is that it will increase our understanding of how these stress responses are involved in antibiotic resistance and the mechanisms used by bacteria to colonize the gut.KEYWORDS envelope stress response, NADH dehydrogenase I, cytochrome bo 3 , membrane protein biogenesis, Cpx envelope stress response, NADH dehydrogenase, cytochrome oxidase, inner membrane, protein complex, protein folding, protein localization, respiration, two-component regulatory systems G ram-negative bacteria are characterized by the structure of their cell envelope, which consists of the inner membrane (IM), the outer membrane, and the peptidoglycan layer within the periplasmic space. Of these, the IM contains the greatest protein diversity (1). Proteins that reside within the IM...

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“…In these cases, it is sufficient to report a change in the relative levels of biomolecules in the analysed samples. However, in other cases, it is critical to provide the results in absolute units (concentration units such as moles per litre, or amount units such as moles) [14][15][16]. Although the progress in quantitative MS method development and applications has been enormous, still a lot of effort has to be made to render MS a fully quantitative tool.…”

Section: Plu 0000-0003-3471-045xmentioning

confidence: 99%

Quantitative mass spectrometry: an overview

Urban

2016

Phil. Trans. R. Soc. A.

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Mass spectrometry (MS) is a mainstream chemical analysis technique in the twenty-first century. It has contributed to numerous discoveries in chemistry, physics and biochemistry. Hundreds of research laboratories scattered all over the world use MS every day to investigate fundamental phenomena on the molecular level. MS is also widely used by industry—especially in drug discovery, quality control and food safety protocols. In some cases, mass spectrometers are indispensable and irreplaceable by any other metrological tools. The uniqueness of MS is due to the fact that it enables direct identification of molecules based on the mass-to-charge ratios as well as fragmentation patterns. Thus, for several decades now, MS has been used in qualitative chemical analysis. To address the pressing need for quantitative molecular measurements, a number of laboratories focused on technological and methodological improvements that could render MS a fully quantitative metrological platform. In this theme issue, the experts working for some of those laboratories share their knowledge and enthusiasm about quantitative MS. I hope this theme issue will benefit readers, and foster fundamental and applied research based on quantitative MS measurements. This article is part of the themed issue ‘Quantitative mass spectrometry’.

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The quantitative and condition-dependent Escherichia coli proteome

Cited by 708 publications

References 58 publications

A yield-cost tradeoff governs Escherichia coli's decision between fermentation and respiration in carbon-limited growth

A yield-cost tradeoff governs Escherichia coli's decision between fermentation and respiration in carbon-limited growth

A Bacterial Stress Response Regulates Respiratory Protein Complexes To Control Envelope Stress Adaptation

Quantitative mass spectrometry: an overview

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