Alkaline stress inhibits the growth of Staphylococcus epidermidis by inducing TCA cycle-triggered ROS production

2021 ◽  
Author(s):  
Tomotaka Ohkubo ◽  
Yasuhiko Matsumoto ◽  
Yuki Ogasawara ◽  
Takashi Sugita
Keyword(s):  
Staphylococcus Epidermidis ◽  
Tca Cycle ◽  
Alkaline Stress ◽  
Ros Production

scholarly journals Staphylococcus epidermidis Polysaccharide Intercellular Adhesin Production Significantly Increases during Tricarboxylic Acid Cycle Stress

2005 ◽  
Vol 187 (9) ◽  
pp. 2967-2973 ◽  
Author(s):  
Cuong Vuong ◽  
Joshua B. Kidder ◽  
Erik R. Jacobson ◽  
Michael Otto ◽  
Richard A. Proctor ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Redox Status ◽  
Tricarboxylic Acid ◽  
Polysaccharide Intercellular Adhesin ◽  
Low Oxygen ◽  
Acid Cycle ◽  
The Tca Cycle ◽  
High Concentrations

ABSTRACT Staphylococcal polysaccharide intercellular adhesin (PIA) is important for the development of a mature biofilm. PIA production is increased during growth in a nutrient-replete or iron-limited medium and under conditions of low oxygen availability. Additionally, stress-inducing stimuli such as heat, ethanol, and high concentrations of salt increase the production of PIA. These same environmental conditions are known to repress tricarboxylic acid (TCA) cycle activity, leading us to hypothesize that altering TCA cycle activity would affect PIA production. Culturing Staphylococcus epidermidis with a low concentration of the TCA cycle inhibitor fluorocitrate dramatically increased PIA production without impairing glucose catabolism, the growth rate, or the growth yields. These data lead us to speculate that one mechanism by which staphylococci perceive external environmental change is through alterations in TCA cycle activity leading to changes in the intracellular levels of biosynthetic intermediates, ATP, or the redox status of the cell. These changes in the metabolic status of the bacteria result in the attenuation or augmentation of PIA production.

scholarly journals Optimal Coupling of Hepatic Mitochondrial Metabolism with Lipogenesis Promotes Healthy Embryonic to Post-hatch Development in Chicken (FS03-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chaitra Surugihalli ◽  
Angela Chan ◽  
Meghan Maguire ◽  
Linda Farley ◽  
Hsiao-Ching Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Oxidation ◽  
Insulin Signaling ◽  
Oxidative Metabolism ◽  
Tca Cycle ◽  
Hepatic Insulin Resistance ◽  
Ros Production ◽  
Alcoholic Fatty Liver ◽  
Optimal Coupling ◽  
Mitochondrial Oxidative Metabolism

Abstract Objectives With 90% of the energy derived from yolk lipid oxidation in late-term embryos, and the dramatic induction of lipogenesis post-hatch, the liver is subjected to intense lipid burden during embryonic to post-hatch transition in chicken. Interestingly, unlike in rodents and humans with non-alcoholic fatty liver disease, this metabolic milieu in chicken embryos and hatchlings is not thought to promote metabolic syndrome or oxidative stress. We hypothesized that the optimal coupling of hepatic mitochondrial oxidative metabolism and lipogenesis will support insulin signaling and prevent onset of oxidative stress. Methods Fertile eggs (64 ± 3 g) were incubated at 38 °C and 45% relative humidity. At embryonic days (e), e14, e18 and post-hatch days (ph), ph3 and ph7, serum and tissues were collected for metabolic analysis. Hepatic mitochondria was isolated and incubated with [13C3]pyruvate to determine tricarboxylic acid (TCA) cycle activity and reactive oxygen species (ROS) production. Results Serum ketones (µM ± SEM) were significantly higher (P < 0.01) during e14 (3237 ± 189) and e18 (3944 ± 503) and reduced dramatically after hatch (ph3; 381 ± 42, ph7; 322 ± 60). Conversely, hepatic triglycerides (mg/g ± SEM) significantly increased from e14 (2.3 ± 0.6) and e18 (7.4 ± 1.2) to ph3 (93.6 ± 11.79) and ph7 (92 ± 14). Genes regulating lipid oxidation and lipogenesis paralleled the changes in ketones and liver triglycerides respectively. Further, hepatic mitochondrial activity during e18 and ph3 was significantly higher compared to e14, as determined by the rates of 13C incorporation into the TCA cycle intermediates. Interestingly, lipotoxic intermediates (ceramides, diacylglycerols) and inflammatory markers (IL6, TNFA) remained unchanged through e14 to ph7, while ROS production decreased from e14 to ph7. Phosphorylation rates of AKT in the liver was progressively higher from e14 through ph7, suggesting robust insulin signaling. Conclusions These results illustrate optimal coupling between mitochondrial oxidative metabolism, lipogenesis and insulin signaling, thus preventing the onset of oxidative stress during embryonic to post-hatch development. Embryonic to neonatal transition in chicken could be a valuable model to investigate mechanisms regulating mitochondrial lipid oxidation, lipogenesis and onset of hepatic insulin resistance. Funding Sources National Institutes of Health.

scholarly journals A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of Staphylococcus epidermidis During β-Lactam Stress

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Vinai Chittezham Thomas ◽  
Lauren C. Kinkead ◽  
Ashley Janssen ◽  
Carolyn R. Schaeffer ◽  
Keith M. Woods ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Citric Acid ◽  
Cell Surface ◽  
Staphylococcus Epidermidis ◽  
Citric Acid Cycle ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Content Type ◽  
Acid Cycle

ABSTRACT A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these antibiotics. The increased protection from β-lactam antibiotics could result from pleiotropic effects of a dysfunctional TCA cycle, including increased resistance to oxidative stress, reduced susceptibility to autolysis, and a more positively charged cell surface. IMPORTANCE Staphylococcus epidermidis, a normal inhabitant of the human skin microflora, is the most common cause of indwelling medical device infections. In the present study, we analyzed 126 clinical S. epidermidis isolates and discovered that tricarboxylic acid (TCA) cycle dysfunctions are relatively common in the clinical environment. We determined that a dysfunctional TCA cycle enables S. epidermidis to resist oxidative stress and alter its cell surface properties, making it less susceptible to β-lactam antibiotics.

scholarly journals CcpA coordinates central metabolism and biofilm formation in Staphylococcus epidermidis

Microbiology ◽  
2011 ◽  
Vol 157 (12) ◽  
pp. 3458-3468 ◽  
Author(s):  
Marat R. Sadykov ◽  
Torsten Hartmann ◽  
Theodoric A. Mattes ◽  
Megan Hiatt ◽  
Naja J. Jann ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Protein A ◽  
Tca Cycle ◽  
Gram Positive Bacteria ◽  
Catabolite Control Protein A ◽  
The Tca Cycle ◽  
Laci Repressor ◽  
Modest Effect ◽  
Catabolite Control

Staphylococcus epidermidis is an opportunistic bacterium whose infections often involve the formation of a biofilm on implanted biomaterials. In S. epidermidis, the exopolysaccharide facilitating bacterial adherence in a biofilm is polysaccharide intercellular adhesin (PIA), whose synthesis requires the enzymes encoded within the intercellular adhesin operon (icaADBC). In vitro, the formation of S. epidermidis biofilms is enhanced by conditions that repress tricarboxylic acid (TCA) cycle activity, such as growth in a medium containing glucose. In many Gram-positive bacteria, repression of TCA cycle genes in response to glucose is accomplished by catabolite control protein A (CcpA). CcpA is a member of the GalR–LacI repressor family that mediates carbon catabolite repression, leading us to hypothesize that catabolite control of S. epidermidis biofilm formation is indirectly regulated by CcpA-dependent repression of the TCA cycle. To test this hypothesis, ccpA deletion mutants were constructed in strain 1457 and 1457-acnA and the effects on TCA cycle activity, biofilm formation and virulence were assessed. As anticipated, deletion of ccpA derepressed TCA cycle activity and inhibited biofilm formation; however, ccpA deletion had only a modest effect on icaADBC transcription. Surprisingly, deletion of ccpA in strain 1457-acnA, a strain whose TCA cycle is inactive and where icaADBC transcription is derepressed, strongly inhibited icaADBC transcription. These observations demonstrate that CcpA is a positive effector of biofilm formation and icaADBC transcription and a repressor of TCA cycle activity.

scholarly journals Mitochondrial superoxide and coenzyme Q in insulin-deficient rats: increased electron leak

2011 ◽  
Vol 301 (6) ◽  
pp. R1616-R1624 ◽  
Author(s):  
Judith A. Herlein ◽  
Brian D. Fink ◽  
Dorlyne M. Henry ◽  
Mark A. Yorek ◽  
Lynn M. Teesch ◽  
...  
Keyword(s):  
Weight Loss ◽  
Electron Transport ◽  
Coenzyme Q ◽  
Tca Cycle ◽  
Diabetic Rats ◽  
Superoxide Production ◽  
Ros Production ◽  
Mitochondrial Superoxide ◽  
Respiratory Parameters

Mitochondrial superoxide is important in the pathogeneses of diabetes and its complications. However, there is uncertainty regarding the intrinsic propensity of mitochondria to generate this radical. Studies to date suggest that superoxide production by mitochondria of insulin-sensitive target tissues of insulin-deficient rodents is reduced or unchanged. Moreover, little is known of the role of the Coenzyme Q (CoQ), whose semiquinone form reacts with molecular oxygen to generate superoxide. We measured reactive oxygen species (ROS) production, respiratory parameters, and CoQ content in mitochondria from gastrocnemius muscle of control and streptozotocin (STZ)-diabetic rats. CoQ content did not differ between mitochondria isolated from vehicle- or STZ-treated animals. CoQ also was unaffected by weight loss in the absence of diabetes (induced by caloric restriction). Under state 4 or state 3 conditions, both respiration and ROS release were reduced in diabetic mitochondria fueled with succinate, glutamate plus malate, or with all three substrates (continuous TCA cycle). However, H2O2 and directly measured superoxide production were substantially increased in gastrocnemius mitochondria of diabetic rats when expressed per unit oxygen consumed. On the basis of substrate and inhibitor effects, the mechanism involved multiple electron transport sites. More limited results using heart mitochondria were similar. ROS per unit respiration was greater in muscle mitochondria from diabetic compared with control rats during state 3, as well as state 4, while the reduction in ROS per unit respiration on transition to state 3 was less for diabetic mitochondria. In summary, ROS production is, in fact, increased in mitochondria from insulin-deficient muscle when considered relative to electron transport. This is evident on multiple energy substrates and in different respiratory states. CoQ is not reduced in diabetic mitochondria or with weight loss due to food restriction. The implications of these findings are discussed.

scholarly journals Tricarboxylic Acid Cycle-Dependent Regulation of Staphylococcus epidermidis Polysaccharide Intercellular Adhesin Synthesis

2008 ◽  
Vol 190 (23) ◽  
pp. 7621-7632 ◽  
Author(s):  
Marat R. Sadykov ◽  
Michael E. Olson ◽  
Steven Halouska ◽  
Yefei Zhu ◽  
Paul D. Fey ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Tricarboxylic Acid Cycle ◽  
Signal Transduction Pathway ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Metabolic Status ◽  
Polysaccharide Intercellular Adhesin ◽  
Nutritional Conditions ◽  
The Tca Cycle ◽  
Cycle Dependent

ABSTRACT Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting immunocompromised individuals or those with implanted biomaterials (e.g., catheters). Biomaterial-associated infections often involve the formation of a biofilm on the surface of the medical device. In S. epidermidis, polysaccharide intercellular adhesin (PIA) is an important mediator of biofilm formation and pathogenesis. Synthesis of PIA is regulated by at least three DNA binding proteins (IcaR, SarA, and σB) and several environmental and nutritional conditions. Previously, we observed the environmental conditions that increased PIA synthesis decreased tricarboxylic acid (TCA) cycle activity. In this study, S. epidermidis TCA cycle mutants were constructed, and the function of central metabolism in PIA biosynthesis was examined. TCA cycle inactivation altered the metabolic status of S. epidermidis, resulting in a massive derepression of PIA biosynthetic genes and a redirection of carbon from growth into PIA biosynthesis. These data demonstrate that the bacterial metabolic status is a critical regulatory determinant of PIA synthesis. In addition, these data lead us to propose that the TCA cycle acts as a signal transduction pathway to translate external environmental cues into intracellular metabolic signals that modulate the activity of transcriptional regulators.

scholarly journals Comprehensive Succinylome Profiling Reveals the Pivotal Role of Lysine Succinylation in Energy Metabolism and Quorum Sensing of Staphylococcus epidermidis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiping Zhao ◽  
Yang Han ◽  
Yuzhe Sun ◽  
Zhendong Wei ◽  
Jialong Chen ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Quorum Sensing ◽  
Staphylococcus Epidermidis ◽  
Tca Cycle ◽  
Metabolic Processes ◽  
Go Annotation ◽  
Affinity Enrichment ◽  
Blast Analysis ◽  
Lysine Succinylation ◽  
Key Enzyme

BackgroundLysine succinylation is a newly identified posttranslational modification (PTM), which exists widely from prokaryotes to eukaryotes and participates in various cellular processes, especially in the metabolic processes. Staphylococcus epidermidis is a commensal bacterium in the skin, which attracts more attention as a pathogen, especially in immunocompromised patients and neonates by attaching to medical devices and forming biofilms. However, the significance of lysine succinylation in S. epidermidis proteins has not been investigated.ObjectivesThe purpose of this study was to investigate the physiological and pathological processes of S. epidermidis at the level of PTM. Moreover, by analyzing previous succinylome datasets in various organisms, we tried to provide an in-depth understanding of lysine succinylation.MethodsUsing antibody affinity enrichment followed by LC-MS/MS analysis, we examined the succinylome of S. epidermidis (ATCC 12228). Then, bioinformatics analysis was performed, including Gene Ontology (GO), KEGG enrichment, motif characterization, secondary structure, protein–protein interaction, and BLAST analysis.ResultsA total of 1557 succinylated lysine sites in 649 proteins were identified in S. epidermidis (ATCC 12228). Among these succinylation proteins, GO annotation showed that proteins related to metabolic processes accounted for the most. KEGG pathway characterization indicated that proteins associated with the glycolysis/gluconeogenesis and citrate cycle (TCA cycle) pathway were more likely to be succinylated. Moreover, 13 conserved motifs were identified. The specific motif KsuD was conserved in model prokaryotes and eukaryotes. Succinylated proteins with this motif were highly enriched in the glycolysis/gluconeogenesis pathway. One succinylation site (K144) was identified in S-ribosylhomocysteine lyase, a key enzyme in the quorum sensing system, indicating the regulatory role succinylation may play in bacterial processes. Furthermore, 15 succinyltransferases and 18 desuccinylases (erasers) were predicted in S. epidermidis by BLAST analysis.ConclusionWe performed the first comprehensive profile of succinylation in S. epidermidis and illustrated the significant role succinylation may play in energy metabolism, QS system, and other bacterial behaviors. This study may be a fundamental basis to investigate the underlying mechanisms of colonization, virulence, and infection of S. epidermidis, as well as provide a new insight into regulatory effects succinylation may lay on metabolic processes (Data are available via ProteomeXchange with identifier PXD022866).

scholarly journals Two-Component Signal Transduction System SaeRS Positively RegulatesStaphylococcus epidermidisGlucose Metabolism

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Qiang Lou ◽  
Yijun Qi ◽  
Yuanfang Ma ◽  
Di Qu
Keyword(s):  
Signal Transduction ◽  
Staphylococcus Epidermidis ◽  
Gel Electrophoresis ◽  
Laser Desorption ◽  
Tca Cycle ◽  
Wild Type ◽  
Signal Transduction System ◽  
Two Dimensional Gel Electrophoresis ◽  
Two Component ◽  
Two Component Signal Transduction

Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, we performed a proteomic analysis of differences in expression between theS. epidermidis1457 wild-type andsaeRSmutant to identify candidates regulated by saeRS using two-dimensional gel electrophoresis (2-DE) combined with matrix-assisted laser desorption/lonization mass spectrometry (MALDI-TOF-MS). Of 55 identified proteins that significantly differed in expression between the two strains, 15 were upregulated and 40 were downregulated. The downregulated proteins included enzymes related to glycolysis and TCA cycle, suggesting that glucose is not properly utilized inS. epidermidiswhensaeRSwas deleted. The study will be helpful for treatment ofS. epidermidisinfection from the viewpoint of metabolic modulation dependent on two-component signal transduction system SaeRS.

Scanning Electron Microscopy of Staphylococcus Epidermidis Adherence to Continuous Ambulatory Peritoneal Dialysis Catheters

1985 ◽  
Vol 43 ◽  
pp. 520-521
Author(s):  
William J. Lamoreaux ◽  
David L. Smalley ◽  
Larry M. Baddour ◽  
Alfred P. Kraus
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Staphylococcus Epidermidis ◽  
Sterile Saline ◽  
Intravascular Devices ◽  
Capd Patient ◽  
Scanning Electron

Infections associated with the use of intravascular devices have been documented and have been reported to be related to duration of catheter usage. Recently, Eaton et al. reported that Staphylococcus epidermidis may attach to silastic catheters used in continuous ambulatory peritoneal dialysis (CAPD) treatment. The following study presents findings using scanning electron microscopy (SEM) of S. epidermidis adherence to silastic catheters in an in vitro model. In addition, sections of polyvinyl chloride (PVC) dialysis bags were also evaluated by SEM.The S. epidermidis strain RP62A which had been obtained in a previous outbreak of coagulase-negative staphylococcal sepsis at local hospitals was used in these experiments. The strain produced surface slime on exposure to glucose, whereas a nonadherent variant RP62A-NA, which was also used in these studies, failed to produce slime. Strains were grown overnight on blood agar plates at 37°C, harvested from the surface and resuspended in sterile saline (0.85%), centrifuged (3,000 rpm for 10 minutes) and then washed twice in 0.1 M phosphate-buffered saline at pH 7.0. Organisms were resuspended at a concentration of ca. 106 CFU/ml in: a) sterile unused dianeal at 4.25% dextrose, b) sterile unused dianeal at 1.5% dextrose, c) sterile used dialysate previously containing 4.25% dextrose taken from a CAPD patient, and d) sterile used dialysate previously containing 1.5% dextrose taken from a CAPD patient.

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