scholarly journals Physiological and Transcriptional Responses of Different Industrial Microbes at Near-Zero Specific Growth Rates

2015 ◽  
Vol 81 (17) ◽  
pp. 5662-5670 ◽  
Author(s):  
Onur Ercan ◽  
Markus M. M. Bisschops ◽  
Wout Overkamp ◽  
Thomas R. Jørgensen ◽  
Arthur F. Ram ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Rates ◽  
Microbial Growth ◽  
Current Knowledge ◽  
Product Formation ◽  
Natural Ecosystems ◽  
Transcriptional Responses ◽  
Content Type ◽  
Growth Physiology ◽  
Zero Growth

ABSTRACTThe current knowledge of the physiology and gene expression of industrially relevant microorganisms is largely based on laboratory studies under conditions of rapid growth and high metabolic activity. However, in natural ecosystems and industrial processes, microbes frequently encounter severe calorie restriction. As a consequence, microbial growth rates in such settings can be extremely slow and even approach zero. Furthermore, uncoupling microbial growth from product formation, while cellular integrity and activity are maintained, offers perspectives that are economically highly interesting. Retentostat cultures have been employed to investigate microbial physiology at (near-)zero growth rates. This minireview compares information from recent physiological and gene expression studies on retentostat cultures of the industrially relevant microorganismsLactobacillus plantarum,Lactococcus lactis,Bacillus subtilis,Saccharomyces cerevisiae, andAspergillus niger. Shared responses of these organisms to (near-)zero growth rates include increased stress tolerance and a downregulation of genes involved in protein synthesis. Other adaptations, such as changes in morphology and (secondary) metabolite production, were species specific. This comparison underlines the industrial and scientific significance of further research on microbial (near-)zero growth physiology.

scholarly journals Dynamics in Copy Numbers of Five Plasmids of a DairyLactococcus lactisStrain under Dairy-Related Conditions Including Near-Zero Growth Rates

2018 ◽  
Vol 84 (11) ◽  
Author(s):  
Oscar van Mastrigt ◽  
Marcel M. A. N. Lommers ◽  
Yorick C. de Vries ◽  
Tjakko Abee ◽  
Eddy J. Smid
Keyword(s):  
Nutrient Limitation ◽  
Lactococcus Lactis ◽  
Growth Rates ◽  
Copy Number ◽  
Plasmid Copy ◽  
Content Type ◽  
Copy Numbers ◽  
Wide Range ◽  
Zero Growth ◽  
The Impact

ABSTRACTLactic acid bacteria can carry multiple plasmids affecting their performance in dairy fermentations. The expression of plasmid-borne genes and the activity of the corresponding proteins are severely affected by changes in the numbers of plasmid copies. We studied the impact of growth rate on the dynamics of plasmid copy numbers at high growth rates in chemostat cultures and down to near-zero growth rates in retentostat cultures. Five plasmids of the dairy strainLactococcus lactisFM03-V1 were selected, and these varied in size (3 to 39 kb), in replication mechanism (theta or rolling circle), and in putative (dairy-associated) functions. The copy numbers ranged from 1.5 to 40.5, and the copy number of theta-type replicating plasmids was negatively correlated to the plasmid size. Despite the extremely wide range of growth rates (0.0003 h−1to 0.6 h−1), the copy numbers of the five plasmids were stable and only slightly increased at near-zero growth rates, showing that the plasmid replication rate was strictly controlled. One low-copy-number plasmid, carrying a large exopolysaccharide gene cluster, was segregationally unstable during retentostat cultivations, reflected in a complete loss of the plasmid in one of the retentostat cultures. The copy number of the five plasmids was also hardly affected by varying the pH value, nutrient limitation, or the presence of citrate (maximum 2.2-fold), signifying the stability in copy number of the plasmids.IMPORTANCELactococcus lactisis extensively used in starter cultures for dairy fermentations. Important traits for the growth and survival ofL. lactisin dairy fermentations are encoded by genes located on plasmids, such as genes involved in lactose and citrate metabolism, protein degradation, oligopeptide uptake, and bacteriophage resistance. Because the number of plasmid copies could affect the expression of plasmid-borne genes, it is important to know the factors that influence the plasmid copy numbers. We monitored the plasmid copy numbers ofL. lactisat near-zero growth rates, characteristic for cheese ripening. Moreover, we analyzed the effects of pH, nutrient limitation, and the presence of citrate. This showed that the plasmid copy numbers were stable, giving insight into plasmid copy number dynamics in dairy fermentations.

scholarly journals Polymorphonuclear Leukocytes Restrict Growth of Pseudomonas aeruginosa in the Lungs of Cystic Fibrosis Patients

2014 ◽  
Vol 82 (11) ◽  
pp. 4477-4486 ◽  
Author(s):  
Kasper N. Kragh ◽  
Morten Alhede ◽  
Peter Ø. Jensen ◽  
Claus Moser ◽  
Thomas Scheike ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Growth Rates ◽  
Polymorphonuclear Leukocytes ◽  
Growth Patterns ◽  
Tissue Samples ◽  
Content Type ◽  
Growth Physiology

ABSTRACTCystic fibrosis (CF) patients have increased susceptibility to chronic lung infections byPseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate thein vivogrowth physiology ofP. aeruginosawithin lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescencein situhybridization (PNA-FISH)-based method was used to estimate thein vivogrowth rates ofP. aeruginosadirectly in lung tissue samples from CF patients and the growth rates ofP. aeruginosain infected lungs in a mouse model. The growth rate ofP. aeruginosawithin CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect onP. aeruginosaby PMNs was also observedin vitro, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding thatP. aeruginosagrowth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O2consumption, which slows the growth ofP. aeruginosain infected CF lungs. In support of this, the growth ofP. aeruginosawas significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronicP. aeruginosainfection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration.

scholarly journals Pichia pastoris Exhibits High Viability and a Low Maintenance Energy Requirement at Near-Zero Specific Growth Rates

2016 ◽  
Vol 82 (15) ◽  
pp. 4570-4583 ◽  
Author(s):  
Corinna Rebnegger ◽  
Tim Vos ◽  
Alexandra B. Graf ◽  
Minoska Valli ◽  
Jack T. Pronk ◽  
...  
Keyword(s):  
Pichia Pastoris ◽  
Growth Rates ◽  
Specific Growth ◽  
Energy Requirement ◽  
Maintenance Energy ◽  
Content Type ◽  
Chemostat Cultures ◽  
Zero Growth ◽  
Maintenance Energy Requirement ◽  
Specific Growth Rates

ABSTRACTThe yeastPichia pastorisis a widely used host for recombinant protein production. Understanding its physiology at extremely low growth rates is a first step in the direction of decoupling product formation from cellular growth and therefore of biotechnological relevance. Retentostat cultivation is an excellent tool for studying microbes at extremely low specific growth rates but has so far not been implemented forP. pastoris. Retentostat feeding regimes were based on the maintenance energy requirement (mS) and maximum biomass yield on glucose (YX/Smax) estimated from steady-state glucose-limited chemostat cultures. Aerobic retentostat cultivation enabled reproducible, smooth transitions from a specific growth rate (μ) of 0.025 h−1to near-zero specific growth rates (μ < 0.001 h−1). At these near-zero specific growth rates, viability remained at least 97%. The value ofmSat near-zero growth rates was 3.1 ± 0.1 mg glucose per g biomass and h, which was 3-fold lower than themSestimated from faster-growing chemostat cultures. This difference indicated thatP. pastorisreduces its maintenance energy requirement at extremely low μ, a phenomenon not previously observed in eukaryotes. Intracellular levels of glycogen and trehalose increased, while μ progressively declined during retentostat cultivation. Transcriptional reprogramming toward zero growth included the upregulation of many transcription factors as well as stress-related genes and the downregulation of cell cycle genes. This study underlines the relevance of comparative analysis of maintenance energy metabolism, which has an important impact on large-scale industrial processes.IMPORTANCEThe yeastPichia pastorisnaturally lives on trees and can utilize different carbon sources, among them glucose, glycerol, and methanol. In biotechnology, it is widely used for the production of recombinant proteins. For both the understanding of life in its natural habitat and optimized production processes, a better understanding of cell physiology at an extremely low growth rate would be of extraordinary value. Therefore, we have grownP. pastorisin a retentostat, which allows the cultivation of metabolically active cells even at zero growth. Here we reached doubling times as long as 38 days and found thatP. pastorisdecreases its maintenance energy demand 3-fold during very slow growth, which enables it to survive with a much lower substrate supply than baker's yeast.

scholarly journals Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida

2017 ◽  
Vol 83 (7) ◽  
Author(s):  
Klara Bojanovič ◽  
Isotta D'Arrigo ◽  
Katherine S. Long
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Pseudomonas Putida ◽  
Cellular Response ◽  
Functional Characterization ◽  
Transcriptional Response ◽  
Stress Conditions ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Content Type

ABSTRACTBacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response ofPseudomonas putidaKT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through whichP. putidaresponds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings.IMPORTANCEThis study maps the complete transcriptional response ofP. putidaKT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one condition, suggesting their involvement in adaptation to stress conditions and identifying interesting candidates for further functional characterization.

scholarly journals Stenotrophomonas maltophiliaDifferential Gene Expression in Synthetic Cystic Fibrosis Sputum Reveals Shared and Cystic Fibrosis Strain-Specific Responses to the Sputum Environment

2019 ◽  
Vol 201 (15) ◽  
Author(s):  
Graham G. Willsey ◽  
Korin Eckstrom ◽  
Annette E. LaBauve ◽  
Lauren A. Hinkel ◽  
Kristin Schutz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Stress Responses ◽  
Metabolic Pathways ◽  
Stenotrophomonas Maltophilia ◽  
Acute Infection ◽  
Survival Strategies ◽  
Transcriptional Responses ◽  
Content Type ◽  
Insight Into

ABSTRACTStenotrophomonas maltophiliais a Gram-negative opportunistic pathogen that can infect the lungs of people with cystic fibrosis (CF). The highly viscous mucus in the CF lung, expectorated as sputum, serves as the primary nutrient source for microbes colonizing this site and induces virulence-associated phenotypes and gene expression in several CF pathogens. Here, we characterized the transcriptional responses of threeS. maltophiliastrains during exposure to synthetic CF sputum medium (SCFM2) to gain insight into how this organism interacts with the host in the CF lung. These efforts led to the identification of 881 transcripts differentially expressed by all three strains, many of which reflect the metabolic pathways used byS. maltophiliain sputum, as well as altered stress responses. The latter correlated with increased resistance to peroxide exposure after pregrowth in SCFM2 for two of the strains. We also compared the SCFM2 transcriptomes of twoS. maltophiliaCF isolates to that of the acute infection strain,S. maltophiliaK279a, allowing us to identify CF isolate-specific signatures in differential gene expression. The expression of genes from the accessory genomes was also differentially altered in response to SCFM2. Finally, a number of biofilm-associated genes were differentially induced in SCFM2, particularly in K279a, which corresponded to increased aggregation and biofilm formation in this strain relative to both CF strains. Collectively, this work details the response ofS. maltophiliato an environment that mimics important aspects of the CF lung, identifying potential survival strategies and metabolic pathways used byS. maltophiliaduring infections.IMPORTANCEStenotrophomonas maltophiliais an important infecting bacterium in the airways of people with cystic fibrosis (CF). However, compared to the other CF pathogens,S. maltophiliahas been relatively understudied. The significance of our research is to provide insight into the global transcriptomic changes ofS. maltophiliain response to a medium that was designed to mimic important aspects of the CF lung. This study elucidates the overall metabolic changes that occur whenS. maltophiliaencounters the CF lung and generates a road map of candidate genes to test usingin vitroandin vivomodels of CF.

scholarly journals Molecular and Metabolic Adaptations of Lactococcus lactis at Near-Zero Growth Rates

2014 ◽  
Vol 81 (1) ◽  
pp. 320-331 ◽  
Author(s):  
Onur Ercan ◽  
Michiel Wels ◽  
Eddy J. Smid ◽  
Michiel Kleerebezem
Keyword(s):  
Amino Acids ◽  
Lactococcus Lactis ◽  
Growth Rates ◽  
Low Carbon ◽  
Content Type ◽  
Growth State ◽  
Mixed Acid ◽  
Metabolic Adaptations ◽  
Zero Growth ◽  
Growth Adaptation

ABSTRACTThis paper describes the molecular and metabolic adaptations ofLactococcus lactisduring the transition from a growing to a near-zero growth state by using carbon-limited retentostat cultivation. Transcriptomic analyses revealed that metabolic patterns shifted between lactic- and mixed-acid fermentations during retentostat cultivation, which appeared to be controlled at the level of transcription of the corresponding pyruvate dissipation-encoding genes. During retentostat cultivation, cells continued to consume several amino acids but also produced specific amino acids, which may derive from the conversion of glycolytic intermediates. We identify a novel motif containing CTGTCAG in the upstream regions of several genes related to amino acid conversion, which we propose to be the target site for CodY inL. lactisKF147. Finally, under extremely low carbon availability, carbon catabolite repression was progressively relieved and alternative catabolic functions were found to be highly expressed, which was confirmed by enhanced initial acidification rates on various sugars in cells obtained from near-zero-growth cultures. The present integrated transcriptome and metabolite (amino acids and previously reported fermentation end products) study provides molecular understanding of the adaptation ofL. lactisto conditions supporting low growth rates and expands our earlier analysis of the quantitative physiology of this bacterium at near-zero growth rates toward gene regulation patterns involved in zero-growth adaptation.

scholarly journals Subcellular Architecture of the xyl Gene Expression Flow of the TOL Catabolic Plasmid of Pseudomonas putida mt-2

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Juhyun Kim ◽  
Angel Goñi-Moreno ◽  
Víctor de Lorenzo
Keyword(s):  
Gene Expression ◽  
Pseudomonas Putida ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Tol Plasmid ◽  
Content Type ◽  
Catabolic Plasmid ◽  
Species Specific ◽  
Translation Coupling ◽  
Bacterial Cytoplasm

ABSTRACT Despite intensive research on the biochemical and regulatory features of the archetypal catabolic TOL system borne by pWW0 of Pseudomonas putida strain mt-2, the physical arrangement and tridimensional logic of the xyl gene expression flow remains unknown. In this work, the spatial distribution of specific xyl mRNAs with respect to the host nucleoid, the TOL plasmid, and the ribosomal pool has been investigated. In situ hybridization of target transcripts with fluorescent oligonucleotide probes revealed that xyl mRNAs cluster in discrete foci, adjacent but clearly separated from the TOL plasmid and the cell nucleoid. Also, they colocalize with ribosome-rich domains of the intracellular milieu. This arrangement was maintained even when the xyl genes were artificially relocated to different chromosomal locations. The same held true when genes were expressed through a heterologous T7 polymerase-based system, which likewise led to mRNA foci outside the DNA. In contrast, rifampin treatment, known to ease crowding, blurred the confinement of xyl transcripts. This suggested that xyl mRNAs exit from their initiation sites to move to ribosome-rich points for translation—rather than being translated coupled to transcription. Moreover, the results suggest the distinct subcellular motion of xyl mRNAs results from both innate properties of the sequences and the physical forces that keep the ribosomal pool away from the nucleoid in P. putida. This scenario is discussed within the background of current knowledge on the three-dimensional organization of the gene expression flow in other bacteria and the environmental lifestyle of this soil microorganism. IMPORTANCE The transfer of information between DNA, RNA, and proteins in a bacterium is often compared to the decoding of a piece of software in a computer. However, the tridimensional layout and the relational logic of the cognate biological hardware, i.e., the nucleoid, the RNA polymerase, and the ribosomes, are habitually taken for granted. In this work, we inspected the localization and fate of the transcripts that stem from the archetypal biodegradative plasmid pWW0 of soil bacterium Pseudomonas putida strain KT2440 through the nonhomogeneous milieu of the bacterial cytoplasm. The results expose that—similarly to computers—the material components that enable the expression flow are well separated physically and they decipher the sequences through a distinct tridimensional arrangement with no indication of transcription/translation coupling. We argue that the resulting subcellular architecture enters an extra regulatory layer that obeys a species-specific positional code and accompanies the environmental lifestyle of this bacterium.

scholarly journals Normal Adaptation of Candida albicans to the Murine Gastrointestinal Tract Requires Efg1p-Dependent Regulation of Metabolic and Host Defense Genes

2012 ◽  
Vol 12 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Jessica V. Pierce ◽  
Daniel Dignard ◽  
Malcolm Whiteway ◽  
Carol A. Kumamoto
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Ectopic Expression ◽  
Dependent Manner ◽  
Null Mutant ◽  
Gi Tract ◽  
Transcriptional Responses ◽  
Content Type ◽  
Opportunistic Fungal Pathogen ◽  
Mutant Cells

ABSTRACTAlthough gastrointestinal colonization by the opportunistic fungal pathogenCandida albicansis generally benign, severe systemic infections are thought to arise due to escape of commensalC. albicansfrom the gastrointestinal (GI) tract. TheC. albicanstranscription factor Efg1p is a major regulator of GI colonization, hyphal morphogenesis, and virulence. The goals of this study were to identify the Efg1p regulon during GI tract colonization and to compareC. albicansgene expression during colonization of different organs of the GI tract. Our results identified significant differences in gene expression between cells colonizing the cecum and ileum. During colonization,efg1−null mutant cells expressed higher levels of genes involved in lipid catabolism, carnitine biosynthesis, and carnitine utilization than did colonizing wild-type (WT) cells. In addition, during laboratory growth,efg1−null mutant cells grew to a higher density than WT cells. Theefg1−null mutant grew in depleted medium, while WT cells could grow only if the depleted medium was supplemented with carnitine, a compound that promotes the metabolism of fatty acids. Altered gene expression and altered growth capability support the ability ofefg1−cells to hypercolonize naïve mice. Also, Efg1p was shown to be important for transcriptional responses to the stresses present in the cecum environment. For example, during colonization,SOD5, encoding a superoxide dismutase, was highly upregulated in an Efg1p-dependent manner. Ectopic expression ofSOD5in anefg1−null mutant increased the fitness of theefg1−null mutant cells during colonization. These data show thatEFG1is an important regulator of GI colonization.

scholarly journals Quantitative Physiology of Non-Energy-Limited Retentostat Cultures of Saccharomyces cerevisiae at Near-Zero Specific Growth Rates

2019 ◽  
Vol 85 (20) ◽  
Author(s):  
Yaya Liu ◽  
Anissa el Masoudi ◽  
Jack T. Pronk ◽  
Walter M. van Gulik
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Growth Rates ◽  
Phosphate Limitation ◽  
High Yield ◽  
Content Type ◽  
Fermentation Processes ◽  
Yield Production ◽  
Zero Growth ◽  
Limited Supply ◽  
High Yield Production

ABSTRACT So far, the physiology of Saccharomyces cerevisiae at near-zero growth rates has been studied in retentostat cultures with a growth-limiting supply of the carbon and energy source. Despite its relevance in nature and industry, the near-zero growth physiology of S. cerevisiae under conditions where growth is limited by the supply of non-energy substrates remains largely unexplored. This study analyzes the physiology of S. cerevisiae in aerobic chemostat and retentostat cultures grown under either ammonium or phosphate limitation. To compensate for loss of extracellular nitrogen- or phosphorus-containing compounds, establishing near-zero growth rates (μ < 0.002 h−1) in these retentostats required addition of low concentrations of ammonium or phosphate to reservoir media. In chemostats as well as in retentostats, strongly reduced cellular contents of the growth-limiting element (nitrogen or phosphorus) and high accumulation levels of storage carbohydrates were observed. Even at near-zero growth rates, culture viability in non-energy-limited retentostats remained above 80% and ATP synthesis was still sufficient to maintain an adequate energy status and keep cells in a metabolically active state. Compared to similar glucose-limited retentostat cultures, the nitrogen- and phosphate-limited cultures showed aerobic fermentation and a partial uncoupling of catabolism and anabolism. The possibility to achieve stable, near-zero growth cultures of S. cerevisiae under nitrogen or phosphorus limitation offers interesting prospects for high-yield production of bio-based chemicals. IMPORTANCE The yeast Saccharomyces cerevisiae is a commonly used microbial host for production of various biochemical compounds. From a physiological perspective, biosynthesis of these compounds competes with biomass formation in terms of carbon and/or energy equivalents. Fermentation processes functioning at extremely low or near-zero growth rates would prevent loss of feedstock to biomass production. Establishing S. cerevisiae cultures in which growth is restricted by the limited supply of a non-energy substrate therefore could have a wide range of industrial applications but remains largely unexplored. In this work we accomplished near-zero growth of S. cerevisiae through limited supply of a non-energy nutrient, namely, the nitrogen or phosphorus source, and carried out a quantitative physiological study of the cells under these conditions. The possibility to achieve near-zero-growth S. cerevisiae cultures through limited supply of a non-energy nutrient may offer interesting prospects to develop novel fermentation processes for high-yield production of bio-based chemicals.

scholarly journals Modeling thePseudomonasSulfur Regulome by Quantifying the Storage and Communication of Information

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Peter E. Larsen ◽  
Sarah Zerbs ◽  
Philip D. Laible ◽  
Frank R. Collart ◽  
Peter Korajczyk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Information Theory ◽  
Information Transfer ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Transcriptional Responses ◽  
Content Type

ABSTRACTBacteria are not simply passive consumers of nutrients or merely steady-state systems. Rather, bacteria are active participants in their environments, collecting information from their surroundings and processing and using that information to adapt their behavior and optimize survival. The bacterial regulome is the set of physical interactions that link environmental information to the expression of genes by way of networks of sensors, transporters, signal cascades, and transcription factors. As bacteria cannot have one dedicated sensor and regulatory response system for every possible condition that they may encounter, the sensor systems must respond to a variety of overlapping stimuli and collate multiple forms of information to make “decisions” about the most appropriate response to a specific set of environmental conditions. Here, we analyzePseudomonas fluorescenstranscriptional responses to multiple sulfur nutrient sources to generate a predictive, computational model of the sulfur regulome. To model the regulome, we utilize a transmitter-channel-receiver scheme of information transfer and utilize principles from information theory to portrayP. fluorescensas an informatics system. This approach enables us to exploit the well-established metrics associated with information theory to model the sulfur regulome. Our computational modeling analysis results in the accurate prediction of gene expression patterns in response to the specific sulfur nutrient environments and provides insights into the molecular mechanisms ofPseudomonassensory capabilities and gene regulatory networks. In addition, modeling the bacterial regulome using the tools of information theory is a powerful and generalizable approach that will have multiple future applications to other bacterial regulomes.IMPORTANCEBacteria sense and respond to their environments using a sophisticated array of sensors and regulatory networks to optimize their fitness and survival in a constantly changing environment. Understanding how these regulatory and sensory networks work will provide the capacity to predict bacterial behaviors and, potentially, to manipulate their interactions with an environment or host. Leveraging the information theory provides useful quantitative metrics for modeling the information processing capacity of bacterial regulatory networks. As our model accurately predicted gene expression profiles in a bacterial model system, we posit that the information theory-based approaches will be important to enhance our understanding of a wide variety of bacterial regulomes and our ability to engineer bacterial sensory and regulatory networks.

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