scholarly journals Nitrogen starvation induces persister cell formation inEscherichia coli

2018 ◽  
Author(s):  
Daniel R. Brown

AbstractTo cope with fluctuations in their environment bacteria have evolved multiple adaptive stress responses. One such response is the nitrogen regulation stress response, which allows bacteria such asEscherichia colito cope with and overcome conditions of nitrogen limitation. This response is directed by the two-component system NtrBC, where NtrC acts as the major transcriptional regulator to activate the expression of genes to mount the response. Recently we showed that NtrC directly regulates the expression of therelAgene, the major (p)ppGpp synthetase inE. coli, coupling the nitrogen regulation stress and stringent responses. As elevated levels of (p)ppGpp have been implicated in the formation persister cells, here we investigated whether nitrogen starvation promotes their formation and whether the NtrC-RelA regulatory cascade plays a role in this. The results reveal that both nitrogen starvedE. coliform a higher percentage of persister cells than non-starved cells, and that both NtrC and RelA are important for this process. This provides novel insights into how the formation of persisters can be promoted in response to a nutritional stress.ImportanceBacteria often reside in environments where nutrient availability is scarce and therefore they have evolved adaptive responses to rapidly cope with conditions of feast and famine. Understanding the mechanisms that underpin the regulation of how bacteria cope with this stress is a fundamentally important question in the wider context of understanding the biology of the bacterial cell and bacterial pathogenesis. Two major adaptive mechanisms to cope with starvation are the nitrogen regulation (ntr) stress and stringent responses. Here I describe how these bacterial stress responses are coordinated under conditions of nitrogen starvation to promote the formation of antibiotic tolerant persister cells by elevating levels of the secondary messenger (p)ppGpp.

2018 ◽  
Vol 201 (3) ◽  
Author(s):  
Daniel R. Brown

ABSTRACTTo cope with fluctuations in their environment, bacteria have evolved multiple adaptive stress responses. One such response is the nitrogen regulation stress response, which allows bacteria, such asEscherichia coli, to cope with and overcome conditions of nitrogen limitation. This response is directed by the two-component system NtrBC, where NtrC acts as the major transcriptional regulator to activate the expression of genes to mount the response. Recently, my colleagues and I showed that NtrC directly regulates the expression of therelAgene, the major (p)ppGpp synthetase inE. coli, coupling the nitrogen regulation stress and stringent responses. As elevated levels of (p)ppGpp have been implicated in the formation of persister cells, here, I investigated whether nitrogen starvation promotes their formation and whether the NtrC-RelA regulatory cascade plays a role. The results reveal that nitrogen-starvedE. colisynthesizes (p)ppGpp and forms a higher percentage of persister cells than nonstarved cells and that both NtrC and RelA are important for these processes. This study provides novel insights into how the formation of persisters can be promoted in response to a nutritional stress.IMPORTANCEBacteria often reside in environments where nutrient availability is scarce; therefore, they have evolved adaptive responses to rapidly cope with conditions of feast and famine. Understanding the mechanisms that underpin the regulation of how bacteria cope with this stress is a fundamentally important question in the wider context of understanding the biology of the bacterial cell and bacterial pathogenesis. Two major adaptive mechanisms to cope with starvation are the nitrogen regulation (ntr) stress and stringent responses. Here, I describe how these bacterial stress responses are coordinated under conditions of nitrogen starvation to promote the formation of antibiotic-tolerant persister cells by elevating levels of the secondary messenger (p)ppGpp.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jin-Xing Liao ◽  
Kai-Huai Li ◽  
Jin-Pei Wang ◽  
Jia-Ru Deng ◽  
Qiong-Guang Liu ◽  
...  

Abstract Background Xanthomonas citri pv. citri (Xcc) is a citrus canker causing Gram-negative bacteria. Currently, little is known about the biological and molecular responses of Xcc to low temperatures. Results Results depicted that low temperature significantly reduced growth and increased biofilm formation and unsaturated fatty acid (UFA) ratio in Xcc. At low temperature Xcc formed branching structured motility. Global transcriptome analysis revealed that low temperature modulates multiple signaling networks and essential cellular processes such as carbon, nitrogen and fatty acid metabolism in Xcc. Differential expression of genes associated with type IV pilus system and pathogenesis are important cellular adaptive responses of Xcc to cold stress. Conclusions Study provides clear insights into biological characteristics and genome-wide transcriptional analysis based molecular mechanism of Xcc in response to low temperature.


2018 ◽  
Vol 46 (6) ◽  
pp. 1721-1728 ◽  
Author(s):  
Amy Switzer ◽  
Daniel R. Brown ◽  
Sivaramesh Wigneshweraraj

Bacterial adaptive responses to biotic and abiotic stresses often involve large-scale reprogramming of the transcriptome. Since nitrogen is an essential component of the bacterial cell, the transcriptional basis of the adaptive response to nitrogen starvation has been well studied. The adaptive response to N starvation in Escherichia coli is primarily a ‘scavenging response’, which results in the transcription of genes required for the transport and catabolism of nitrogenous compounds. However, recent genome-scale studies have begun to uncover and expand some of the intricate regulatory complexities that underpin the adaptive transcriptional response to nitrogen starvation in E. coli. The purpose of this review is to highlight some of these new developments.


2021 ◽  
Author(s):  
Anastasia Gant Kanegusuku ◽  
Isidora N. Stankovic ◽  
Pamela A. Cote-Hammarlof ◽  
Priscilla H. Yong ◽  
Christine A. White-Ziegler

One of the first environmental cues sensed by a microbe as it enters a human host is an upshift in temperature to 37°C. In this dynamic timepoint analysis, we demonstrate that this environmental transition rapidly signals a multitude of gene expression changes in Escherichia coli . Bacteria grown at 23°C under aerobic conditions were shifted to 37°C and mRNA expression was measured at timepoints after the shift to 37°C (t=0.5, 1, and 4 hours). The first hour is characterized by a transient shift to anaerobic respiration strategies and stress responses, particularly acid resistance, indicating that temperature serves as a sentinel cue to predict and prepare for various niches within the host. The temperature effects on a subset of stress response genes were shown to be mediated by RpoS, directly correlated with RpoS, DsrA and RprA levels, and increased acid resistance was observed that was dependent on 23°C growth and RpoS. By 4 hours, gene expression shifted to aerobic respiration pathways, decreased stress responses, coupled with increases in genes associated with biosynthesis (amino acid, nucleotides), iron uptake, and host defense. ompT , a gene that confers resistance to antimicrobial peptides, was highly thermoregulated and with a pattern conserved in enteropathogenic and uropathogenic E. coli . An immediate decrease in curli gene expression concomitant with an increase in flagellar gene expression implicates temperature in this developmental decision. Together, our studies demonstrate that temperature signals a reprogramming of gene expression immediately upon an upshift that may predict, prepare, and benefit survival of the bacterium within the host. IMPORTANCE: As one of the first cues sensed by the microbe upon entry into a human host, understanding how bacteria like E. coli modulate gene expression in response to temperature improves our understanding of how bacteria immediately initiate responses beneficial to survival and colonization. For pathogens, understanding the various pathways of thermal regulation could yield valuable targets for anti-infective chemotherapeutic drugs or disinfection measures. In addition, our data provide a dynamic examination of the RpoS stress response, providing genome-wide support for how temperature impacts RpoS through changes in RpoS stability and modulation by small regulatory RNAs.


2020 ◽  
Vol 9 (1) ◽  
pp. 96-107
Author(s):  
A. D. Filev ◽  
V. M. Pisarev

ABSTRACT. Defining molecules with high prognostic value for predicting the course and outcomes of life-threatening sepsis, severe injuries, vascular accidents remains an urgent problem in emergency medicine. One of the promising candidate biomarkers of emergency states and critical illness is the content of extracellular DNA (exDNA) in blood plasma. The purpose of this review is to identify the prospects for the introduction of cfDNA in clinical medicine and the severities arose along this way. The levels and altered dynamics of the concentration of circulating DNA fragments, including the organ-specific fraction of exDNA seem informative today for assessing the degree of damage to the organ of interest, the probability of a complicated course and the prognosis of outcomes of emergency/critical illness in Intensive Care Unit (ICU) patients. Sources of exDNA circulating in the bloodstream may include the nuclei of dying cells from organs and tissues, damaged mitochondria, the pool of which should be remodeled with mitophagy, as well as microorganisms. Similarly to pathogen-associated molecules (PAMP) represented by fragments of bacterial and viral DNA, native DNA molecules associated with damage (DAMP) bind to toll-like receptors (TLR9) and intracellular DNA sensors (cGAS-STING, NLRP3), initiating the inflammatory processes in tissues and hemostatic disorders. These processes represent natural adaptive responses protecting against microbes, as well as disadaptation responses potentiating cell damage in organs. The increasing expression of genes encoding proinflammatory signaling pathways associated with NF-kB transcription factor and interferon-regulating factors (IRF), in turn, contribute to production of cytokines and other factors enhancing the stress-responses that alter the functional activity of cells in various organs. The available literature data suggest that the quantitative determining plasma exDNA, which serves as PAMP and DAMP to significantly contribute to pathogenesis of emergency states and critical illness, might aid in predicting the outcome and justifying the in-time personalization of treatment of emergency and post-emergency patients.


2021 ◽  
Vol 9 (2) ◽  
pp. 249
Author(s):  
Thomas Schalck ◽  
Bram Van den Bergh ◽  
Jan Michiels

Fuels and polymer precursors are widely used in daily life and in many industrial processes. Although these compounds are mainly derived from petrol, bacteria and yeast can produce them in an environment-friendly way. However, these molecules exhibit toxic solvent properties and reduce cell viability of the microbial producer which inevitably impedes high product titers. Hence, studying how product accumulation affects microbes and understanding how microbial adaptive responses counteract these harmful defects helps to maximize yields. Here, we specifically focus on the mode of toxicity of industry-relevant alcohols, terpenoids and aromatics and the associated stress-response mechanisms, encountered in several relevant bacterial and yeast producers. In practice, integrating heterologous defense mechanisms, overexpressing native stress responses or triggering multiple protection pathways by modifying the transcription machinery or small RNAs (sRNAs) are suitable strategies to improve solvent tolerance. Therefore, tolerance engineering, in combination with metabolic pathway optimization, shows high potential in developing superior microbial producers.


2021 ◽  
Vol 22 (5) ◽  
pp. 2529
Author(s):  
Amin Javadifar ◽  
Sahar Rastgoo ◽  
Maciej Banach ◽  
Tannaz Jamialahmadi ◽  
Thomas P. Johnston ◽  
...  

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.


2016 ◽  
Vol 363 (14) ◽  
pp. fnw136 ◽  
Author(s):  
Umji Choi ◽  
Young-Ha Park ◽  
Yeon-Ran Kim ◽  
Yeong-Jae Seok ◽  
Chang-Ro Lee

2022 ◽  
Vol 8 (1) ◽  
pp. 50
Author(s):  
Yifan Li ◽  
Xiya Meng ◽  
Degang Guo ◽  
Jia Gao ◽  
Qiwei Huang ◽  
...  

Light is perceived by photoreceptors in fungi and further integrated into the stress-activated MAPK HOG pathway, and thereby potentially activates the expression of genes for stress responses. This indicates that the precise control of light conditions can likely improve the conidial yield and stress resistance to guarantee the low cost and long shelf life of Trichoderma-based biocontrol agents and biofertilizers. In this study, effects of wavelengths and intensities of light on conidial yield and stress tolerance to osmotic, oxidative and pH stresses in Trichoderma guizhouense were investigated. We found that 2 μmol photons/(m2 × s) of blue light increased the conidial yield more than 1000 folds as compared to dark condition and simultaneously enhanced conidial stress resistance. The enhanced conidial stress resistance is probably due to the upregulated stress-related genes in blue light, which is under the control of the blue light receptor BLR1 and the MAP kinase HOG1.


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