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| Open AccessHigh-resolution temporal profiling of E. coli transcriptional response
Understanding how cells dynamically adapt to their environment is important, but temporal information about cellular behaviour is often limited. Here, Miano et al. apply unsupervised machine learning to a dataset describing the activity of over 1,800 promoters in E. coli, measured every 10 minutes, defining three primary stages of promoter activation in response to heavy metal stress.
- Arianna Miano
- , Kevin Rychel
- & Jeff Hasty
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Article
| Open AccessGenome-wide promoter responses to CRISPR perturbations of regulators reveal regulatory networks in Escherichia coli
Measuring gene expression responses for every transcription factor (TF)-gene pair in living prokaryotic cells is challenging. Here the authors report pooled promoter responses to TF perturbation sequencing (PPTP-seq) using CRISPRi, which they use to address this problem in E. coli.
- Yichao Han
- , Wanji Li
- & Fuzhong Zhang
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Article
| Open AccessFunctional decomposition of metabolism allows a system-level quantification of fluxes and protein allocation towards specific metabolic functions
Quantifying the contribution of individual molecular components to complex cellular processes is a grand challenge in systems biology. Here, the authors present a general theoretical framework (Functional Decomposition of Metabolism, FDM) to quantify the contribution of every metabolic reaction to metabolic functions, e.g. the synthesis of biomass building blocks.
- Matteo Mori
- , Chuankai Cheng
- & Terence Hwa
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Article
| Open AccessQuorum sensing as a mechanism to harness the wisdom of the crowds
Bacteria release and respond to autoinducers in a process known as quorum sensing. While classically viewed as a strategy to coordinate cell behaviour, Moreno-Gámez et al. demonstrate using modelling that quorum sensing may also be used to sense the environment as a collective by pooling information at relevant scales and harnessing the wisdom of the crowds.
- Stefany Moreno-Gámez
- , Michael E. Hochberg
- & G. S. van Doorn
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| Open AccessStress-induced metabolic exchanges between complementary bacterial types underly a dynamic mechanism of inter-species stress resistance
Microbes can cooperate and share resources via metabolic cross-feeding. Here, the authors show that excretion of key metabolites following acid stress provides a collaborative, inter-species mechanism of stress resistance.
- Kapil Amarnath
- , Avaneesh V. Narla
- & Terence Hwa
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Article
| Open AccessDynamic fluctuations in a bacterial metabolic network
The interconnected network of cellular metabolism is potentially prone to generating oscillatory behaviour. Here, the authors use single-cell FRET measurements of pyruvate levels to reveal large periodic fluctuations in bacterial glycolysis.
- Shuangyu Bi
- , Manika Kargeti
- & Victor Sourjik
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Article
| Open AccessStringent response ensures the timely adaptation of bacterial growth to nutrient downshift
Bacteria undergo nutrient fluctuations during repeated feast and famine cycles and need to metabolically adapt to these changes. Using quantitative proteomics, Zhu & Dai show that the stringent response of (p)ppGpp is crucial for the timely adaption of bacterial growth to both amino acid and carbon downshift.
- Manlu Zhu
- & Xiongfeng Dai
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Article
| Open AccessRobust replication initiation from coupled homeostatic mechanisms
Homeostasis of DNA density is a hallmark of living cells. The authors show via mathematical modelling how two cycles, a titration-based concentration cycle and a nucleotide activation cycle, together drive replication in E. coli at all growth rates.
- Mareike Berger
- & Pieter Rein ten Wolde
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Article
| Open AccessAuxotrophic and prototrophic conditional genetic networks reveal the rewiring of transcription factors in Escherichia coli
The bacterium E. coli has around 300 transcriptional factors, but the functions of many of them, and the interactions between their respective regulatory networks, are unclear. Here, the authors study genetic interactions among all transcription factor genes in E. coli, revealing condition-dependent interactions and roles for uncharacterized transcription factors.
- Alla Gagarinova
- , Ali Hosseinnia
- & Mohan Babu
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| Open AccessExtensive regulation of enzyme activity by phosphorylation in Escherichia coli
While phosphorylation is an essential post-translational modification in eukaryotes only recently the phosphoproteome of prokaryotes has been provided. Here, Schastnaya et al. mutate 52 phosphosites on 23 E. coli enzymes and apply metabolomics to provide evidence for the functional relevance of bacterial phosphorylation events.
- Evgeniya Schastnaya
- , Zrinka Raguz Nakic
- & Uwe Sauer
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Article
| Open AccessThe persistence potential of transferable plasmids
Conjugative plasmids mediate the spread and maintenance of diverse traits in microbial communities, but the conditions underlying plasmid persistence are poorly understood. Here, Wang and You present a modeling framework for analysis of gene flow and prediction of plasmid persistence and abundance in complex communities.
- Teng Wang
- & Lingchong You
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Article
| Open AccessA compendium of DNA-binding specificities of transcription factors in Pseudomonas syringae
The authors set out to identify binding motifs for all 301 transcription factors of a plant pathogenic bacterium, Pseudomonas syringae, using HT-SELEX. They successfully identify binding motifs for 100 transcription factors, infer their binding sites on the genome, and validate the predicted interactions and functions.
- Ligang Fan
- , Tingting Wang
- & Xin Deng
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| Open AccessEntropy of a bacterial stress response is a generalizable predictor for fitness and antibiotic sensitivity
Bacterial transcriptomic data have been used to predict antibiotic susceptibility in a species- or antibiotic-specific manner. Here, the authors show that global transcriptional disorder is a common stress response in bacteria with low fitness, and present a general approach that can predict bacterial fitness independently of species or type of stress.
- Zeyu Zhu
- , Defne Surujon
- & Tim van Opijnen
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Article
| Open AccessDiauxie and co-utilization of carbon sources can coexist during bacterial growth in nutritionally complex environments
It is thought that when multiple carbon sources are available, bacteria metabolize them either sequentially or simultaneously. Here, the authors show that a marine bacterium can use a mixed strategy when multiple possible nutrients are provided, and analyse the metabolic pathways involved.
- Elena Perrin
- , Veronica Ghini
- & Marco Fondi
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| Open AccessSequential modification of bacterial chemoreceptors is key for achieving both accurate adaptation and high gain
Bacterial chemoreceptors have multiple methylation sites, but whether the order of methylation matters is unclear. Here, the authors show that sequentially ordered methylation is critical for perfect adaptation and for attenuating the trade-off between accurate adaptation and high response gain.
- Bernardo A. Mello
- , Anderson B. Beserra
- & Yuhai Tu
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Article
| Open AccessPooled CRISPRi screening of the cyanobacterium Synechocystis sp PCC 6803 for enhanced industrial phenotypes
Developing cyanobacteria as CO2-neutral cell factories relies on the knowledge of the regulation mechanisms for growth and metabolism. Here, the authors develop an inducible CRISPRi gene repression library in Synechocystis sp. PCC 6803 and screens genes potentially affecting growth and L-lactate tolerance and production.
- Lun Yao
- , Kiyan Shabestary
- & Elton P. Hudson
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Article
| Open AccessThe Escherichia coli transcriptome mostly consists of independently regulated modules
Mechanistic insight into the regulation of transcriptional modules remains scarce. Here, the authors identify statistically independent gene sets by applying independent component analysis to a high-quality E. coli RNA-seq data compendium and find that most gene sets represent the effects of specific transcriptional regulators.
- Anand V. Sastry
- , Ye Gao
- & Bernhard O. Palsson
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Article
| Open AccessMultisite phosphorylation drives phenotypic variation in (p)ppGpp synthetase-dependent antibiotic tolerance
Individual bacteria within isogenic populations can differ in antibiotic tolerance. Here, Libby et al. show that antibiotic tolerance variability can be driven by ‘noisy’ expression of a gene encoding a (p)ppGpp synthetase, which is in turn regulated by multisite phosphorylation of a transcription factor.
- Elizabeth A. Libby
- , Shlomi Reuveni
- & Jonathan Dworkin
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Article
| Open AccessAn integrated genomic regulatory network of virulence-related transcriptional factors in Pseudomonas aeruginosa
The virulence of Pseudomonas aeruginosa is regulated by many transcriptional factors (TFs). Here, the authors study the crosstalk between 20 key virulence-related TFs, validate 347 functional target genes, and describe the regulatory relationships of the 20 TFs with their targets in a network that is available as an online platform.
- Hao Huang
- , Xiaolong Shao
- & Xin Deng
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Article
| Open AccessMortality causes universal changes in microbial community composition
Environmental stress can affect the outcome of ecological competition. Here, the authors use theory and experiments with a synthetic microbial community to show that a tradeoff between growth rate and competitive ability determines which species prevails when the population faces variable mortality rates.
- Clare I. Abreu
- , Jonathan Friedman
- & Jeff Gore
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| Open AccessGrowth strategy of microbes on mixed carbon sources
Bacteria grown on two carbon sources either consume both sources simultaneously or consume them sequentially. Here the authors use a metabolic network model of E. coli to show that optimal protein resource allocation and topological features of the network can explain the choice of carbon acquisition.
- Xin Wang
- , Kang Xia
- & Chao Tang
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Article
| Open AccessAge structure landscapes emerge from the equilibrium between aging and rejuvenation in bacterial populations
Some daughter cells inherit the maternal old pole during bacterial division, but does this correspond to aging? Here, Proenca et al. show that constant patterns of aging and rejuvenation connect distinct growth equilibria within bacterial clonal populations, providing evidence for deterministic age structures.
- Audrey M. Proenca
- , Camilla Ulla Rang
- & Lin Chao
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| Open AccessHigh protein copy number is required to suppress stochasticity in the cyanobacterial circadian clock
Circadian clocks must maintain their fidelity despite stochasticity arising from finite protein copy numbers. Here, the authors show that a small cyanobacterium relies on an environmentally driven timer likely because its low protein copy numbers cannot support an accurate free-running clock.
- Justin Chew
- , Eugene Leypunskiy
- & Michael J. Rust
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Article
| Open AccessSpatial self-organization resolves conflicts between individuality and collective migration
How bacteria migrate collectively despite individual phenotypic variation is not understood. Here, the authors show that cells spontaneously sort themselves within moving bands such that variations in individual tumble bias, a determinant of gradient climbing speed, are compensated by the local gradient steepness experienced by individuals.
- X. Fu
- , S. Kato
- & T. Emonet
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Article
| Open AccessQuantifying the benefit of a proteome reserve in fluctuating environments
Fast-growing bacteria produce many proteins in excess of what seems optimal for exponential growth. Here, the authors present a mathematical model and experimental evidence supporting that this overexpression serves as a strategic reserve to quickly meet demand upon sudden improvement in growth conditions.
- Matteo Mori
- , Severin Schink
- & Terence Hwa
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| Open AccessNutrient limitation determines the fitness of cheaters in bacterial siderophore cooperation
Cooperative behaviour among individuals provides a collective benefit, but is considered costly. Using Pseudomonas aeruginosa as a model system, the authors show that secretion of the siderophore pyoverdine only incurs a fitness cost and favours cheating when its building blocks carbon or nitrogen are growth-limiting.
- D. Joseph Sexton
- & Martin Schuster
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Article
| Open AccessOptimality and sub-optimality in a bacterial growth law
Organisms improve their fitness by adjusting their gene expression to the environment, for example bacteria scale the expression of metabolic enzymes near linearly to their growth rate. Here, the authors show that such linear scaling often maximizes growth rate, but that linear scaling is suboptimal under some conditions.
- Benjamin D. Towbin
- , Yael Korem
- & Uri Alon
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| Open AccessCentrality in the host–pathogen interactome is associated with pathogen fitness during infection
Hubs tend to be essential for function in protein networks within organisms. Here, the authors show that during infection, it is the proteins with high centrality in theY. pestishost–pathogen interactome that are most important for pathogen fitness during infection, and highlight the importance of pathogen proteins that likely cause significant perturbation of the host interactome.
- Núria Crua Asensio
- , Elisabet Muñoz Giner
- & Marc Torrent Burgas
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Article
| Open AccessSingle-molecule imaging reveals modulation of cell wall synthesis dynamics in live bacterial cells
The bacterial cell wall is important for cell shape and stability, but how the activities of the biosynthetic machinery are coordinated are not clear. Here the authors use single-molecule imaging and chemical perturbations to determine factors that affect the localization dynamics of penicillin-binding proteins (PBP)1A and PBP1B.
- Timothy K. Lee
- , Kevin Meng
- & Kerwyn Casey Huang
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| Open AccessMulti-omics integration accurately predicts cellular state in unexplored conditions for Escherichia coli
Multi-omics data integration is a great challenge. Here, the authors compile a database of E. coliproteomics, transcriptomics, metabolomics and fluxomics data to train models of recurrent neural network and constrained regression, enabling prediction of bacterial responses to perturbations.
- Minseung Kim
- , Navneet Rai
- & Ilias Tagkopoulos
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| Open AccessReconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis
Sigma factors are regulatory proteins that reprogram the bacterial RNA polymerase in response to stress conditions to transcribe certain genes, including those for other sigma factors. Here, Chauhan et al. describe the complete sigma factor regulatory network of the pathogen Mycobacterium tuberculosis.
- Rinki Chauhan
- , Janani Ravi
- & Maria Laura Gennaro
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Article
| Open AccessProteome-wide selected reaction monitoring assays for the human pathogen Streptococcus pyogenes
Selected reaction monitoring mass spectrometry (SRM-MS) can quantify dynamic changes in protein expression with high sensitivity. Karlsson et al. define optimal detection parameters for 10,412 distinct group A Streptococcus pyogenespeptides, which facilitates proteome-wide SRM-MS studies in this bacterium.
- Christofer Karlsson
- , Lars Malmström
- & Johan Malmström