A Simple Screen to Identify Promoters Conferring High Levels of Phenotypic Noise

Freed, Nikki E.; Silander, Olin K.; Stecher, Bärbel; Böhm, Alex; Hardt, Wolf‐Dietrich; Ackermann, Martin

doi:10.1371/journal.pgen.1000307

Cited by 77 publications

(65 citation statements)

References 28 publications

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“…Salmonella serovar Typhimurium is a food-borne pathogen that after ingestion invades the gastrointestinal epithelia, reaching the mesenteric lymph nodes. It then can establish a systemic infection, replicating in the spleen and liver of the host (35,39,45,49,84). During pathogenesis, bacteria encounter several different microenvironments in the host (10), and several bacteria, including Salmonella serovar Typhimurium, effectively adapt by utilizing HKs (5).…”

Section: Discussionmentioning

confidence: 99%

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QseC MediatesSalmonella entericaSerovar Typhimurium VirulenceIn VitroandIn Vivo

2010

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The autoinducer-3 (AI-3)/epinephrine (Epi)/norepinephrine (NE) interkingdom signaling system mediates chemical communication between bacteria and their mammalian hosts. The three signals are sensed by the QseC histidine kinase (HK) sensor. Salmonella enterica serovar Typhimurium is a pathogen that uses HKs to sense its environment and regulate virulence. Salmonella serovar Typhimurium invades epithelial cells and survives within macrophages. Invasion of epithelial cells is mediated by the type III secretion system (T3SS) encoded in Salmonella pathogenicity island 1 (SPI-1), while macrophage survival and systemic disease are mediated by the T3SS encoded in SPI-2. Here we show that QseC plays an important role in Salmonella serovar Typhimurium pathogenicity. A qseC mutant was impaired in flagellar motility, in invasion of epithelial cells, and in survival within macrophages and was attenuated for systemic infection in 129x1/SvJ mice. QseC acts globally, regulating expression of genes within SPI-1 and SPI-2 in vitro and in vivo (during infection of mice). Additionally, dopamine ␤-hydroxylase knockout (Dbh ؊/؊ ) mice that do not produce Epi or NE showed different susceptibility to Salmonella serovar Typhimurium infection than wild-type mice. These data suggest that the AI-3/Epi/NE signaling system is a key factor during Salmonella serovar Typhimurium pathogenesis in vitro and in vivo. Elucidation of the role of this interkingdom signaling system in Salmonella serovar Typhimurium should contribute to a better understanding of the complex interplay between the pathogen and the host during infection.Prokaryotes and eukaryotes achieve cell-to-cell signaling utilizing chemical signals. The signaling systems allow intra-and interspecies and intra-and interkingdom communication (48). The autoinducer-3 (AI-3)/epinephrine (Epi)/norepinephrine (NE) interkingdom signaling system allows communication between bacteria and their mammalian hosts. AI-3 is produced by many bacterial species (80), and Epi and NE are host stress hormones (36,56). This system was first described as a system activating virulence traits in enterohemorrhagic Escherichia coli (EHEC) (55,75). The signals are sensed by histidine sensor kinases (HKs

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Section: Discussionmentioning

confidence: 99%

“…This motility was reported previously to not play a role in Salmonella virulence in vivo (53). However, flagella induce inflammation via Tolllike receptor 5 during Salmonella infection of the intestinal mucosa (32,35,77). During its evolution, Salmonella serovar Typhimurium acquired many pathogenicity islands (57).…”

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confidence: 99%

QseC MediatesSalmonella entericaSerovar Typhimurium VirulenceIn VitroandIn Vivo

2010

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“…This result is interesting in the light of a series of recent studies reporting phenotypic variation between genetically identical bacteria that live in homogeneous environments (4,9,10,22,24,(26)(27)(28). These differences include cell size, interdivision intervals, gene expression, and behavior.…”

Section: Vol 193 2011 Pole Age Affects M Extorquens Cell Size Andmentioning

confidence: 74%

Pole Age Affects Cell Size and the Timing of Cell Division in Methylobacterium extorquens AM1

Bergmiller

Ackermann

2011

J Bacteriol

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A number of recent experiments at the single-cell level have shown that genetically identical bacteria that live in homogeneous environments often show a substantial degree of phenotypic variation between cells. Often, this variation is attributed to stochastic aspects of biology-the fact that many biological processes involve small numbers of molecules and are thus inherently variable. However, not all variation between cells needs to be stochastic in nature; one deterministic process that could be important for cell variability in some bacterial species is the age of the cell poles. Working with the alphaproteobacterium Methylobacterium extorquens, we monitored individuals in clonally growing populations over several divisions and determined the pole age, cell size, and interdivision intervals of individual cells. We observed the high levels of variation in cell size and the timing of cell division that have been reported before. A substantial fraction of this variation could be explained by each cell's pole age and the pole age of its mother: cell size increased with increasing pole age, and the interval between cell divisions decreased. A theoretical model predicted that populations governed by such processes will quickly reach a stable distribution of different age and size classes. These results show that the pole age distribution in bacterial populations can contribute substantially to cellular individuality. In addition, they raise questions about functional differences between cells of different ages and the coupling of cell division to cell size.In several species of alphaproteobacteria, the two cells emerging from division have been shown to be systematically different. First, experiments with Caulobacter crescentus and Sinorhizobium meliloti have shown differences in protein localization between cells with new and old poles (13,29). Second, experiments with several species of alphaproteobacteria have shown that cells with "new" poles are smaller than cells with "old" poles (13), (12). Third, in C. crescentus, cells with increasingly old poles show signs of aging, while new pole cells are rejuvenated (2, 3). Here, we used the alphaproteobacterium Methylobacterium extorquens to investigate whether the age of a cell's poles has a systematic effect on its size and on the timing of cell division.M. extorquens is a facultative methylotroph that is ubiquitous in aquatic and terrestrial environments (15) and is often associated with plants (8). M. extorquens strain AM1 is a genetic model system (31) that shows substantial variation in cell size and interdivision intervals (26, 27) between genetically identical cells. Motivated by these reports on phenotypic variation, we asked three questions about cell size asymmetry and the timing of cell division. First, does cell size increase with pole age? Previous experiments with alphaproteobacteria have only distinguished between "old" and "new" poles (12, 13). If we analyze "old" poles of different ages, do we see a systematic effect of pole age on cell size? Secon...

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“…A screen for noisy promoters in Salmonella enterica showed that some proteins, especially flagellar gene products, show high stochasticity (105). By broadening the range of characters such as motility and environmental stress resistance across a population, high gene expression noise can increase the likelihood that some cells within the population are better able to endure environmental transitions (9,31).…”

Section: Phenotypic Variation Within Populationsmentioning

confidence: 99%

“…Consequently, noise reduction mechanisms preserving the fidelity of regulatory signals may evolve in some cellular functions (21,83). This is borne out by the difference in noise between genes in a genome (105).…”

Section: Phenotypic Variation Within Populationsmentioning

confidence: 99%

Culture History and Population Heterogeneity as Determinants of Bacterial Adaptation: the Adaptomics of a Single Environmental Transition

Ryall

Eydallin

Ferenci

2012

Microbiol Mol Biol Rev

135

109

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SUMMARY Diversity in adaptive responses is common within species and populations, especially when the heterogeneity of the frequently large populations found in environments is considered. By focusing on events in a single clonal population undergoing a single transition, we discuss how environmental cues and changes in growth rate initiate a multiplicity of adaptive pathways. Adaptation is a comprehensive process, and stochastic, regulatory, epigenetic, and mutational changes can contribute to fitness and overlap in timing and frequency. We identify culture history as a major determinant of both regulatory adaptations and microevolutionary change. Population history before a transition determines heterogeneities due to errors in translation, stochastic differences in regulation, the presence of aged, damaged, cheating, or dormant cells, and variations in intracellular metabolite or regulator concentrations. It matters whether bacteria come from dense, slow-growing, stressed, or structured states. Genotypic adaptations are history dependent due to variations in mutation supply, contingency gene changes, phase variation, lateral gene transfer, and genome amplifications. Phenotypic adaptations underpin genotypic changes in situations such as stress-induced mutagenesis or prophage induction or in biofilms to give a continuum of adaptive possibilities. Evolutionary selection additionally provides diverse adaptive outcomes in a single transition and generally does not result in single fitter types. The totality of heterogeneities in an adapting population increases the chance that at least some individuals meet immediate or future challenges. However, heterogeneity complicates the adaptomics of single transitions, and we propose that subpopulations will need to be integrated into future population biology and systems biology predictions of bacterial behavior.

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A Simple Screen to Identify Promoters Conferring High Levels of Phenotypic Noise

Cited by 77 publications

References 28 publications

QseC MediatesSalmonella entericaSerovar Typhimurium VirulenceIn VitroandIn Vivo

QseC MediatesSalmonella entericaSerovar Typhimurium VirulenceIn VitroandIn Vivo

Pole Age Affects Cell Size and the Timing of Cell Division in Methylobacterium extorquens AM1

Culture History and Population Heterogeneity as Determinants of Bacterial Adaptation: the Adaptomics of a Single Environmental Transition

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