scholarly journals Make and break the alarmone: regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria

2019 ◽  
Vol 43 (4) ◽  
pp. 389-400 ◽  
Author(s):  
Séverin Ronneau ◽  
Régis Hallez
Keyword(s):  
Cell Cycle ◽  
Stress Response ◽  
Stress Responses ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Second Messengers ◽  
Molecular Devices ◽  
Environmental Cues ◽  
Fluctuating Environments ◽  
Harsh Conditions

ABSTRACTBacteria use dedicated mechanisms to respond adequately to fluctuating environments and to optimize their chances of survival in harsh conditions. One of the major stress responses used by virtually all bacteria relies on the sharp accumulation of an alarmone, the guanosine penta- or tetra-phosphate commonly referred to as (p)ppGpp. Under stressful conditions, essentially nutrient starvation, these second messengers completely reshape the metabolism and physiology by coordinately modulating growth, transcription, translation and cell cycle. As a central regulator of bacterial stress response, the alarmone is also involved in biofilm formation, virulence, antibiotics tolerance and resistance in many pathogenic bacteria. Intracellular concentrations of (p)ppGpp are determined by a highly conserved and widely distributed family of proteins called RelA-SpoT Homologs (RSH). Recently, several studies uncovering mechanisms that regulate RSH activities have renewed a strong interest in this field. In this review, we outline the diversity of the RSH protein family as well as the molecular devices used by bacteria to integrate and transform environmental cues into intracellular (p)ppGpp levels.

scholarly journals The Rcs System in Enterobacteriaceae: Envelope Stress Responses and Virulence Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiao Meng ◽  
Glenn Young ◽  
Jingyu Chen
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Cell Envelope ◽  
Regulatory System ◽  
Virulence Regulation ◽  
Bacterial Interaction ◽  
Envelope Stress

The bacterial cell envelope is a protective barrier at the frontline of bacterial interaction with the environment, and its integrity is regulated by various stress response systems. The Rcs (regulator of capsule synthesis) system, a non-orthodox two-component regulatory system (TCS) found in many members of the Enterobacteriaceae family, is one of the envelope stress response pathways. The Rcs system can sense envelope damage or defects and regulate the transcriptome to counteract stress, which is particularly important for the survival and virulence of pathogenic bacteria. In this review, we summarize the roles of the Rcs system in envelope stress responses (ESRs) and virulence regulation. We discuss the environmental and intrinsic sources of envelope stress that cause activation of the Rcs system with an emphasis on the role of RcsF in detection of envelope stress and signal transduction. Finally, the different regulation mechanisms governing the Rcs system’s control of virulence in several common pathogens are introduced. This review highlights the important role of the Rcs system in the environmental adaptation of bacteria and provides a theoretical basis for the development of new strategies for control, prevention, and treatment of bacterial infections.

scholarly journals Nutritional Homeostasis in Batch and Steady-State Culture of Yeast

2004 ◽  
Vol 15 (9) ◽  
pp. 4089-4104 ◽  
Author(s):  
Alok J. Saldanha ◽  
Matthew J. Brauer ◽  
David Botstein
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Steady State ◽  
Stress Response ◽  
Stress Responses ◽  
Global Pattern ◽  
Batch Cultures ◽  
Cycle Arrest ◽  
Chemostat Cultures ◽  
Limiting Nutrient

We studied the physiological response to limitation by diverse nutrients in batch and steady-state (chemostat) cultures of S. cerevisiae. We found that the global pattern of transcription in steady-state cultures in limiting phosphate or sulfate is essentially identical to that of batch cultures growing in the same medium just before the limiting nutrient is completely exhausted. The massive stress response and complete arrest of the cell cycle that occurs when nutrients are fully exhausted in batch cultures is not observed in the chemostat, indicating that the cells in the chemostat are “poor, not starving.” Similar comparisons using leucine or uracil auxotrophs limited on leucine or uracil again showed patterns of gene expression in steady-state closely resembling those of corresponding batch cultures just before they exhaust the nutrient. Although there is also a strong stress response in the auxotrophic batch cultures, cell cycle arrest, if it occurs at all, is much less uniform. Many of the differences among the patterns of gene expression between the four nutrient limitations are interpretable in light of known involvement of the genes in stress responses or in the regulation or execution of particular metabolic pathways appropriate to the limiting nutrient. We conclude that cells adjust their growth rate to nutrient availability and maintain homeostasis in the same way in batch and steady state conditions; cells in steady-state cultures are in a physiological condition normally encountered in batch cultures.

An Overview of Molecular Stress Response Mechanisms in Escherichia coli Contributing to Survival of Shiga Toxin–Producing Escherichia coli during Raw Milk Cheese Production

2011 ◽  
Vol 74 (5) ◽  
pp. 849-864 ◽  
Author(s):  
SILVIO PENG ◽  
TAURAI TASARA ◽  
JÖRG HUMMERJOHANN ◽  
ROGER STEPHAN
Keyword(s):  
Escherichia Coli ◽  
Stress Response ◽  
Foodborne Pathogens ◽  
Stress Responses ◽  
Shiga Toxin ◽  
Pathogenic Bacteria ◽  
Raw Milk ◽  
Heat Shock Stress ◽  
Raw Milk Cheese ◽  
Cheese Production

The ability of foodborne pathogens to survive in certain foods mainly depends on stress response mechanisms. Insight into molecular properties enabling pathogenic bacteria to survive in food is valuable for improvement of the control of pathogens during food processing. Raw milk cheeses are a potential source for human infections with Shiga toxin–producing Escherichia coli (STEC). In this review, we focused on the stress response mechanisms important for allowing STEC to survive raw milk cheese production processes. The major components and regulation pathways for general, acid, osmotic, and heat shock stress responses in E. coli and the implications of these responses for the survival of STEC in raw milk cheeses are discussed.

scholarly journals c-di-AMP-Regulated K+ Importer KtrAB Affects Biofilm Formation, Stress Response, and SpeB Expression in Streptococcus pyogenes

2021 ◽  
Vol 89 (4) ◽  
Author(s):  
Sabrina Faozia ◽  
Tazin Fahmi ◽  
Gary C. Port ◽  
Kyu Hong Cho
Keyword(s):  
Stress Response ◽  
Streptococcus Pyogenes ◽  
Stress Responses ◽  
Biofilm Formation ◽  
Growth Conditions ◽  
Infection Model ◽  
Wild Type ◽  
Content Type ◽  
Double Deletion ◽  
A Subunit

ABSTRACT The second messenger cyclic di-AMP (c-di-AMP) controls biofilm formation, stress response, and virulence in Streptococcus pyogenes. The deletion of the c-di-AMP synthase gene, dacA, results in pleiotropic effects including reduced expression of the secreted protease SpeB. Here, we report a role for K+ transport in c-di-AMP-mediated SpeB expression. The deletion of ktrB in the ΔdacA mutant restores SpeB expression. KtrB is a subunit of the K+ transport system KtrAB that forms a putative high-affinity K+ importer. KtrB forms a membrane K+ channel, and KtrA acts as a cytosolic gating protein that controls the transport capacity of the system by binding ligands including c-di-AMP. SpeB induction in the ΔdacA mutant by K+ specific ionophore treatment also supports the importance of cellular K+ balance in SpeB production. The ΔdacA ΔktrB double deletion mutant not only produces wild-type levels of SpeB but also partially or fully reverts the defective ΔdacA phenotypes of biofilm formation and stress responses, suggesting that many ΔdacA phenotypes are due to cellular K+ imbalance. However, the null pathogenicity of the ΔdacA mutant in a murine subcutaneous infection model is not restored by ktrB deletion, suggesting that c-di-AMP controls not only cellular K+ balance but also other metabolic and/or virulence pathways. The deletion of other putative K+ importer genes, kup and kimA, does not phenocopy the deletion of ktrB regarding SpeB induction in the ΔdacA mutant, suggesting that KtrAB is the primary K+ importer that is responsible for controlling cellular K+ levels under laboratory growth conditions.

scholarly journals RelZ-Mediated Stress Response in Mycobacterium smegmatis: pGpp Synthesis and Its Regulation

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Anushya Petchiappan ◽  
Sujay Y. Naik ◽  
Dipankar Chatterji
Keyword(s):  
Stress Response ◽  
Mycobacterium Smegmatis ◽  
Biofilm Formation ◽  
Second Messengers ◽  
Antibiotic Tolerance ◽  
Response Mechanism ◽  
Term Survival ◽  
Content Type ◽  
Guanosine Tetraphosphate

ABSTRACT Stringent response is a conserved stress response mechanism in which bacteria employ the second messengers guanosine tetraphosphate and guanosine pentaphosphate [collectively termed (p)ppGpp] to reprogram their cellular processes under stress. In mycobacteria, these alarmones govern a multitude of cellular phenotypes, such as cell division, biofilm formation, antibiotic tolerance, and long-term survival. Mycobacterium smegmatis possesses the bifunctional RelMsm as a (p)ppGpp synthetase and hydrolase. In addition, it contains a short alarmone synthetase MS_RHII-RSD (renamed RelZ), which contains an RNase H domain in tandem with the (p)ppGpp synthetase domain. The physiological functions of RelMsm have been well documented, but there is no clear picture about the cellular functions of RelZ in M. smegmatis. RelZ has been implicated in R-loop induced stress response due to its unique domain architecture. In this study, we elucidate the differential substrate utilization pattern of RelZ compared to that of RelMsm. We unveil the ability of RelZ to use GMP as a substrate to synthesize pGpp, thereby expanding the repertoire of second messengers known in mycobacteria. We have demonstrated that the pGpp synthesis activity of RelZ is negatively regulated by RNA and pppGpp. Furthermore, we investigated its role in biofilm formation and antibiotic tolerance. Our findings highlight the complex role played by the RelZ in cellular physiology of M. smegmatis and sheds light upon its functions distinct from those of RelMsm. IMPORTANCE Bacteria utilize nucleotide messengers to survive the hostile environmental conditions and the onslaught of attacks within the host. The second messengers guanosine tetraphosphate and pentaphosphate [(p)ppGpp] have a profound impact on the long-term survival, biofilm formation, antibiotic tolerance, virulence, and pathogenesis of bacteria. Therefore, understanding the stress response mechanism regulated by (p)ppGpp is essential for discovering inhibitors of stress response and potential drug targets. Mycobacterium smegmatis contains two (p)ppGpp synthetases: RelMsm and RelZ. Our study unravels the novel regulatory mechanisms of RelZ activity and its role in mediating antibiotic tolerance. We further reveal its ability to synthesize novel second messenger pGpp, which may have regulatory roles in mycobacteria.

scholarly journals Evo-physio: on stress responses and the earliest land plants

2020 ◽  
Vol 71 (11) ◽  
pp. 3254-3269 ◽  
Author(s):  
Janine M R Fürst-Jansen ◽  
Sophie de Vries ◽  
Jan de Vries
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Plant Cells ◽  
Land Plant ◽  
Land Plants ◽  
Comparative Approach ◽  
Environmental Cues ◽  
Evolutionary Event ◽  
Shed Light ◽  
Genetic Toolkit

Abstract Embryophytes (land plants) can be found in almost any habitat on the Earth’s surface. All of this ecologically diverse embryophytic flora arose from algae through a singular evolutionary event. Traits that were, by their nature, indispensable for the singular conquest of land by plants were those that are key for overcoming terrestrial stressors. Not surprisingly, the biology of land plant cells is shaped by a core signaling network that connects environmental cues, such as stressors, to the appropriate responses—which, thus, modulate growth and physiology. When did this network emerge? Was it already present when plant terrestrialization was in its infancy? A comparative approach between land plants and their algal relatives, the streptophyte algae, allows us to tackle such questions and resolve parts of the biology of the earliest land plants. Exploring the biology of the earliest land plants might shed light on exactly how they overcame the challenges of terrestrialization. Here, we outline the approaches and rationale underlying comparative analyses towards inferring the genetic toolkit for the stress response that aided the earliest land plants in their conquest of land.

Antibiotics Application Strategies to Control Biofilm Formation in Pathogenic Bacteria

2020 ◽  
Vol 21 (4) ◽  
pp. 270-286 ◽  
Author(s):  
Fazlurrahman Khan ◽  
Dung T.N. Pham ◽  
Sandra F. Oloketuyi ◽  
Young-Mog Kim
Keyword(s):  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Extracellular Polymeric Substances ◽  
Quorum Quenching ◽  
Resistance Mechanisms ◽  
Bacterial Biofilm ◽  
Bacterial Cells ◽  
High Concentration ◽  
Biofilm Inhibition ◽  
Abiotic Surfaces

Background: The establishment of a biofilm by most pathogenic bacteria has been known as one of the resistance mechanisms against antibiotics. A biofilm is a structural component where the bacterial community adheres to the biotic or abiotic surfaces by the help of Extracellular Polymeric Substances (EPS) produced by bacterial cells. The biofilm matrix possesses the ability to resist several adverse environmental factors, including the effect of antibiotics. Therefore, the resistance of bacterial biofilm-forming cells could be increased up to 1000 times than the planktonic cells, hence requiring a significantly high concentration of antibiotics for treatment. Methods: Up to the present, several methodologies employing antibiotics as an anti-biofilm, antivirulence or quorum quenching agent have been developed for biofilm inhibition and eradication of a pre-formed mature biofilm. Results: Among the anti-biofilm strategies being tested, the sub-minimal inhibitory concentration of several antibiotics either alone or in combination has been shown to inhibit biofilm formation and down-regulate the production of virulence factors. The combinatorial strategies include (1) combination of multiple antibiotics, (2) combination of antibiotics with non-antibiotic agents and (3) loading of antibiotics onto a carrier. Conclusion: The present review paper describes the role of several antibiotics as biofilm inhibitors and also the alternative strategies adopted for applications in eradicating and inhibiting the formation of biofilm by pathogenic bacteria.

scholarly journals Extract from phyllosphere bacteria with antibiofilm and quorum quenching activity to control several fish pathogenic bacteria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Olivia Nathalia ◽  
Diana Elizabeth Waturangi
Keyword(s):  
Streptococcus Agalactiae ◽  
Aeromonas Hydrophila ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Vibrio Harveyi ◽  
Quorum Quenching ◽  
Indicator Bacteria ◽  
Antibiofilm Activity ◽  
Fish Pathogen ◽  
Phyllosphere Bacteria

Abstract Objective The objective of this research were to screen quorum quenching activity compound from phyllosphere bacteria as well as antibiofilm activity against several fish pathogen bacteria such as Aeromonas hydrophila, Streptococcus agalactiae, and Vibrio harveyi. Results We found eight phyllosphere bacteria isolates with potential quorum quenching activity to inhibit Chromobacterium violaceum as indicator bacteria. Crude extracts (20 mg/mL) showed various antibiofilm activity against fish pathogenic bacteria used in this study. Isolate JB 17B showed the highest activity to inhibit biofilm formation of A. hydrophila and V. harveyi, meanwhile isolate JB 3B showed the highest activity to inhibit biofilm of S. agalactiae. From destruction assay, isolate JB 8F showed the highest activity to disrupt biofilm of A. hydrophila isolate JB 20B showed the highest activity to disrupt biofilm of V. harveyi, isolate JB 17B also showed the highest activity to disrupt biofilm of S. agalactiae.

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

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