scholarly journals Molecular connectivity between extra-cytoplasmic sigma factors and PhoP accounts for integrated mycobacterial stress response

2021 ◽  
Author(s):  
Harsh Goar ◽  
Partha Paul ◽  
Hina Khan ◽  
Dibyendu SARKAR
Keyword(s):  
Stress Response ◽  
Redox Homeostasis ◽  
Regulatory System ◽  
Low Ph ◽  
Sigma Factors ◽  
Ph Homeostasis ◽  
Redox Stress ◽  
Thiol Redox ◽  
Underlying Mechanisms ◽  
Inducible Genes

The main purpose of this study is to understand how mycobacteria can sense numerous stress conditions and mount an appropriate stress response. Recent studies suggest that at low pH M. tuberculosis encounters reductive stress, and in response, modulates redox homeostasis by utilizing the phoPR regulatory system. However, the mechanism of integrated regulation of stress response remains unknown. To probe how PhoP contributes to redox stress response, we find that a PhoP-depleted M. tuberculosis shows a significantly enhanced susceptibility to redox stress relative to the WT bacilli. In keeping with these results, PhoP was shown to contribute to mycothiol redox state. Because SigH, one of the alternative sigma factors of mycobacteria, is known to control expression of redox inducible genes, we probed whether previously-reported PhoP-SigH interaction accounts for mycobacterial redox stress response. We had shown that under acidic conditions PhoP functions in maintaining pH homeostasis via its interaction with SigE. In striking contrast, here we show that under redox stress, direct recruitment of SigH, but not PhoP-SigH interaction, controls expression of mycobacterial thioredoxin genes, a major mycobacterial anti-oxidant system. Together, these unexpected results uncover novel stress-specific enhanced or reduced interaction events of sigma factors and PhoP, as the underlying mechanisms of an adaptive programme, which couples low pH conditions and mycobacterial thiol redox homeostasis.

scholarly journals The Lipid Lysyl-Phosphatidylglycerol Is Present in Membranes of Rhizobium tropici CIAT899 and Confers Increased Resistance to Polymyxin B Under Acidic Growth Conditions

2007 ◽  
Vol 20 (11) ◽  
pp. 1421-1430 ◽  
Author(s):  
Christian Sohlenkamp ◽  
Kanaan A. Galindo-Lagunas ◽  
Ziqiang Guan ◽  
Pablo Vinuesa ◽  
Sally Robinson ◽  
...  
Keyword(s):  
Sinorhizobium Meliloti ◽  
Minimal Medium ◽  
Polymyxin B ◽  
Growth Conditions ◽  
Membrane Lipid ◽  
Low Ph ◽  
Wild Type ◽  
Rhizobium Tropici ◽  
Gram Negative ◽  
Inducible Genes

Lysyl-phosphatidylglycerol (LPG) is a well-known membrane lipid in several gram-positive bacteria but is almost unheard of in gram-negative bacteria. In Staphylococcus aureus, the gene product of mprF is responsible for LPG formation. Low pH-inducible genes, termed lpiA, have been identified in the gram-negative α-proteobacteria Rhizobium tropici and Sinorhizobium medicae in screens for acid-sensitive mutants and they encode homologs of MprF. An analysis of the sequenced bacterial genomes reveals that genes coding for homologs of MprF from S. aureus are present in several classes of organisms throughout the bacterial kingdom. In this study, we show that the expression of lpiA from R. tropici in the heterologous hosts Escherichia coli and Sinorhizobium meliloti causes formation of LPG. A wild-type strain of R. tropici forms LPG (about 1% of the total lipids) when the cells are grown in minimal medium at pH 4.5 but not when grown in minimal medium at neutral pH or in complex tryptone yeast (TY) medium at either pH. LPG biosynthesis does not occur when lpiA is deleted and is restored upon complementation of lpiA-deficient mutants with a functional copy of the lpiA gene. When grown in the low-pH medium, lpiA-deficient rhizobial mutants are over four times more susceptible to the cationic peptide polymyxin B than the wild type.

Difference of MreBCD Complex Interactome in Salmonella Typhimurium ST19 and ST213 Genotypes on Pathogenesis and Stress Response Pathways

2021 ◽  
Vol 22 ◽  
Author(s):  
Reyna Cristina Zepeda-Gurrola ◽  
Gerardo Vázquez-Marrufo ◽  
Xianwu Guo ◽  
Isabel Cristina Rodríguez-Luna ◽  
Alejandro Sánchez-Varela ◽  
...  
Keyword(s):  
Stress Response ◽  
Bacterial Virulence ◽  
Eukaryotic Cells ◽  
Interaction Patterns ◽  
High Infection Rate ◽  
Differential Interaction ◽  
Sequence Variations ◽  
High Infection ◽  
Underlying Mechanisms

: Salmonella enterica is the etiological agent of salmonellosis, with a high infection rate worldwide. In Mexico, ST213 genotype of S. enterica ser. Typhimurium is displacing the ancestral ST19 genotype. Bacterial cytoskeleton protein complex MreBCD play an important role in S. enterica pathogenesis, but underlying mechanisms are unknown. In this study, 106 interactions among MreBCD and 15 proteins from S. Typhimurium Pathogenicity Islands 1 (SP-I) and 2 (SP-2) involved in both bacterial virulence and stress response were predicted in ST213 and ST19 genotypes, of which 12 interactions were confirmed in vitro. In addition, gene cluster analysis in 100 S. Typhimurium genomes was performed for these genes. The in silico and in vitro results showed a novel MreBCD interactome involved in the regulation of pathogenesis and stress response through interactions with virulence factors located at SPI-1 and SPI-2. Furthermore, both pseudogene presence and sequence variations in four tested proteins between genotypes resulted in differential interaction patterns that are involved in Salmonella motility and survival in eukaryotic cells, which could explain replacement of ST19 by ST213 in Mexico.

The role of Akkermansia muciniphila in obesity, diabetes and atherosclerosis

2021 ◽  
Vol 70 (10) ◽  
Author(s):  
Alka Hasani ◽  
Saba Ebrahimzadeh ◽  
Fatemeh Hemmati ◽  
Aytak Khabbaz ◽  
Akbar Hasani ◽  
...  
Keyword(s):  
Type Species ◽  
Anaerobic Bacteria ◽  
Regulatory System ◽  
Content Type ◽  
Akkermansia Muciniphila ◽  
Link Type ◽  
Animal Trials ◽  
Obesity And Diabetes ◽  
Underlying Mechanisms

Alteration in the composition of the gut microbiota can lead to a number of chronic clinical diseases. Akkermansia muciniphila is an anaerobic bacteria constituting 3–5% of the gut microbial community in healthy adults. This bacterium is responsible for degenerating mucin in the gut; its scarcity leads to diverse clinical disorders. In this review, we focus on the role of A. muciniphila in diabetes, obesity and atherosclerosis, as well as the use of this bacterium as a next-generation probiotic. In regard to obesity and diabetes, human and animal trials have shown that A. muciniphila controls the essential regulatory system of glucose and energy metabolism. However, the underlying mechanisms by which A. muciniphila alleviates the complications of obesity, diabetes and atherosclerosis are unclear. At the same time, its abundance suggests improved metabolic disorders, such as metabolic endotoxemia, adiposity insulin resistance and glucose tolerance. The role of A. muciniphila is implicated in declining aortic lesions and atherosclerosis. Well-characterized virulence factors, antigens and cell wall extracts of A. muciniphila may act as effector molecules in these diseases. These molecules may provide novel mechanisms and strategies by which this bacterium could be used as a probiotic for the treatment of obesity, diabetes and atherosclerosis.

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 Cellular Stress in the Pathogenesis of Muscular Disorders—From Cause to Consequence

2020 ◽  
Vol 21 (16) ◽  
pp. 5830 ◽  
Author(s):  
Alexander Mensch ◽  
Stephan Zierz
Keyword(s):  
Stress Response ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
Therapeutic Approaches ◽  
Muscular Disorders ◽  
Adaptive Mechanisms ◽  
Relevant Role ◽  
Pathogenetic Factor ◽  
Underlying Mechanisms

Cellular stress has been considered a relevant pathogenetic factor in a variety of human diseases. Due to its primary functions by means of contractility, metabolism, and protein synthesis, the muscle cell is faced with continuous changes of cellular homeostasis that require rapid and coordinated adaptive mechanisms. Hence, a prone susceptibility to cellular stress in muscle is immanent. However, studies focusing on the cellular stress response in muscular disorders are limited. While in recent years there have been emerging indications regarding a relevant role of cellular stress in the pathophysiology of several muscular disorders, the underlying mechanisms are to a great extent incompletely understood. This review aimed to summarize the available evidence regarding a deregulation of the cellular stress response in individual muscle diseases. Potential mechanisms, as well as involved pathways are critically discussed, and respective disease models are addressed. Furthermore, relevant therapeutic approaches that aim to abrogate defects of cellular stress response in muscular disorders are outlined.

scholarly journals Untargetted Metabolomic Exploration of the Mycobacterium tuberculosis Stress Response to Cinnamon Essential Oil

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 357 ◽  
Author(s):  
Elwira Sieniawska ◽  
Rafał Sawicki ◽  
Joanna Golus ◽  
Milen I. Georgiev
Keyword(s):  
Stress Response ◽  
Essential Oil ◽  
Redox Homeostasis ◽  
Membrane Integrity ◽  
Antimycobacterial Activity ◽  
Stress Factors ◽  
Stress Response System ◽  
Reactive Compound ◽  
Cinnamon Essential Oil ◽  
Cell Wall Permeability

The antimycobacterial activity of cinnamaldehyde has already been proven for laboratory strains and for clinical isolates. What is more, cinnamaldehyde was shown to threaten the mycobacterial plasma membrane integrity and to activate the stress response system. Following promising applications of metabolomics in drug discovery and development we aimed to explore the mycobacteria response to cinnamaldehyde within cinnamon essential oil treatment by untargeted liquid chromatography–mass spectrometry. The use of predictive metabolite pathway analysis and description of produced lipids enabled the evaluation of the stress symptoms shown by bacteria. This study suggests that bacteria exposed to cinnamaldehyde could reorganize their outer membrane as a physical barrier against stress factors. They probably lowered cell wall permeability and inner membrane fluidity, and possibly redirected carbon flow to store energy in triacylglycerols. Being a reactive compound, cinnamaldehyde may also contribute to disturbances in bacteria redox homeostasis and detoxification mechanisms.

Heme Oxygenase as a Therapeutic Funnel in Nutritional Redox Homeostasis and Cellular Stress Response

2009 ◽  
pp. 39-52
Author(s):  
Vittorio Calabrese ◽  
Giovanni Pennisi ◽  
Menotti Calvani ◽  
D. Allan Butterfield ◽  
Cesare Mancuso ◽  
...  
Keyword(s):  
Stress Response ◽  
Heme Oxygenase ◽  
Cellular Stress ◽  
Redox Homeostasis ◽  
Cellular Stress Response

scholarly journals Catalase Expression inAzospirillum brasilenseSp7 Is Regulated by a Network Consisting of OxyR and Two RpoH Paralogs and Including an RpoE1→RpoH5 Regulatory Cascade

2018 ◽  
Vol 84 (23) ◽  
Author(s):  
Ashutosh Kumar Rai ◽  
Sudhir Singh ◽  
Sushil Kumar Dwivedi ◽  
Amit Srivastava ◽  
Parul Pandey ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Sinorhizobium Meliloti ◽  
Deinococcus Radiodurans ◽  
Oxidative Stress Response ◽  
Sigma Factors ◽  
Transcriptional Analysis ◽  
Content Type ◽  
Regulatory Cascade ◽  
Transcription Regulators

ABSTRACTThe genome ofAzospirillum brasilenseencodes five RpoH sigma factors: two OxyR transcription regulators and three catalases. The aim of this study was to understand the role they play during oxidative stress and their regulatory interconnection. Out of the 5 paralogs of RpoH present inA. brasilense, inactivation of onlyrpoH1rendersA. brasilenseheat sensitive. While transcript levels ofrpoH1were elevated by heat stress, those ofrpoH3andrpoH5were upregulated by H2O2. Catalase activity was upregulated inA. brasilenseand itsrpoH::kmmutants in response to H2O2except in the case of therpoH5::kmmutant, suggesting a role for RpoH5 in regulating inducible catalase. Transcriptional analysis of thekatN,katAI, andkatAII genes revealed that the expression ofkatNandkatAII was severely compromised in therpoH3::kmandrpoH5::kmmutants, respectively. Regulation ofkatNandkatAII by RpoH3 and RpoH5, respectively, was further confirmed in anEscherichia colitwo-plasmid system. Regulation ofkatAII by OxyR2 was evident by a drastic reduction in growth, KatAII activity, andkatAII::lacZexpression in anoxyR2::kmmutant. This study reports the involvement of RpoH3 and RpoH5 sigma factors in regulating oxidative stress response in alphaproteobacteria. We also report the regulation of an inducible catalase by a cascade of alternative sigma factors and an OxyR. Out of the three catalases inA. brasilense, those corresponding tokatNandkatAII are regulated by RpoH3 and RpoH5, respectively. The expression ofkatAII is regulated by a cascade of RpoE1→RpoH5 and OxyR2.IMPORTANCEIn silicoanalysis of theA. brasilensegenome showed the presence of multiple paralogs of genes involved in oxidative stress response, which included 2 OxyR transcription regulators and 3 catalases. So far,Deinococcus radioduransandVibrio choleraeare known to harbor two paralogs of OxyR, andSinorhizobium melilotiharbors three catalases. We do not yet know how the expression of multiple catalases is regulated in any bacterium. Here we show the role of multiple RpoH sigma factors and OxyR in regulating the expression of multiple catalases inA. brasilenseSp7. Our work gives a glimpse of systems biology ofA. brasilenseused for responding to oxidative stress.

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