scholarly journals Oxidative Stressors Modify the Response of Streptococcus mutans to Its Competence Signal Peptides

2017 ◽  
Vol 83 (22) ◽  
Author(s):  
Matthew De Furio ◽  
Sang Joon Ahn ◽  
Robert A. Burne ◽  
Stephen J. Hagen

ABSTRACTThe dental caries pathogenStreptococcus mutansis continually exposed to several types of stress in the oral biofilm environment. Oxidative stress generated by reactive oxygen species has a major impact on the establishment, persistence, and virulence ofS. mutans. Here, we combined fluorescent reporter-promoter fusions with single-cell imaging to study the effects of reactive oxygen species on activation of genetic competence inS. mutans. Exposure to paraquat, which generates superoxide anion, produced a qualitatively different effect on activation of expression of the gene for the master competence regulator, ComX, than did treatment with hydrogen peroxide (H2O2), which can yield hydroxyl radical. Paraquat suppressed peptide-mediated induction ofcomXin a progressive and cumulative fashion, whereas the response to H2O2displayed a strong threshold behavior. Low concentrations of H2O2had little effect on induction ofcomXor the bacteriocin genecipB, but expression of these genes declined sharply if extracellular H2O2exceeded a threshold concentration. These effects were not due to decreased reporter gene fluorescence. Two different threshold concentrations were observed in the response to H2O2, depending on the gene promoter that was analyzed and the pathway by which the competence regulon was stimulated. The results show that paraquat and H2O2affect theS. mutanscompetence signaling pathway differently, and that some portions of the competence signaling pathway are more sensitive to oxidative stress than others.IMPORTANCEStreptococcus mutansinhabits the oral biofilm, where it plays an important role in the development of dental caries. Environmental stresses such as oxidative stress influence the growth ofS. mutansand its important virulence-associated behaviors, such as genetic competence.S. mutanscompetence development is a complex behavior that involves two different signaling peptides and can exhibit cell-to-cell heterogeneity. Although oxidative stress is known to influenceS. mutanscompetence, it is not understood how oxidative stress interacts with the peptide signaling or affects heterogeneity. In this study, we used fluorescent reporters to probe the effect of reactive oxygen species on competence signaling at the single-cell level. Our data show that different reactive oxygen species have different effects onS. mutanscompetence, and that some portions of the signaling pathway are more acutely sensitive to oxidative stress than others.

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4138
Author(s):  
Yeon-Jin Cho ◽  
Sun-Hye Choi ◽  
Ra-Mi Lee ◽  
Han-Sung Cho ◽  
Hyewhon Rhim ◽  
...  

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.


2019 ◽  
Vol 201 (22) ◽  
Author(s):  
Laura Barrientos-Moreno ◽  
María Antonia Molina-Henares ◽  
Marta Pastor-García ◽  
María Isabel Ramos-González ◽  
Manuel Espinosa-Urgel

ABSTRACT Iron is essential for most life forms. Under iron-limiting conditions, many bacteria produce and release siderophores—molecules with high affinity for iron—which are then transported into the cell in their iron-bound form, allowing incorporation of the metal into a wide range of cellular processes. However, free iron can also be a source of reactive oxygen species that cause DNA, protein, and lipid damage. Not surprisingly, iron capture is finely regulated and linked to oxidative-stress responses. Here, we provide evidence indicating that in the plant-beneficial bacterium Pseudomonas putida KT2440, the amino acid l-arginine is a metabolic connector between iron capture and oxidative stress. Mutants defective in arginine biosynthesis show reduced production and release of the siderophore pyoverdine and altered expression of certain pyoverdine-related genes, resulting in higher sensitivity to iron limitation. Although the amino acid is not part of the siderophore side chain, addition of exogenous l-arginine restores pyoverdine release in the mutants, and increased pyoverdine production is observed in the presence of polyamines (agmatine and spermidine), of which arginine is a precursor. Spermidine also has a protective role against hydrogen peroxide in P. putida, whereas defects in arginine and pyoverdine synthesis result in increased production of reactive oxygen species. IMPORTANCE The results of this study show a previously unidentified connection between arginine metabolism, siderophore turnover, and oxidative stress in Pseudomonas putida. Although the precise molecular mechanisms involved have yet to be characterized in full detail, our data are consistent with a model in which arginine biosynthesis and the derived pathway leading to polyamine production function as a homeostasis mechanism that helps maintain the balance between iron uptake and oxidative-stress response systems.


2016 ◽  
Vol 198 (11) ◽  
pp. 1563-1575 ◽  
Author(s):  
Kieran D. Collins ◽  
Tessa M. Andermann ◽  
Jenny Draper ◽  
Lisa Sanders ◽  
Susan M. Williams ◽  
...  

ABSTRACTCytoplasmic chemoreceptors are widespread among prokaryotes but are far less understood than transmembrane chemoreceptors, despite being implicated in many processes. One such cytoplasmic chemoreceptor isHelicobacter pyloriTlpD, which is required for stomach colonization and drives a chemotaxis response to cellular energy levels. Neither the signals sensed by TlpD nor its molecular mechanisms of action are known. We report here that TlpD functions independently of the other chemoreceptors. When TlpD is the sole chemoreceptor, it is able to localize to the pole and recruits CheW, CheA, and at least two CheV proteins to this location. It loses the normal membrane association that appears to be driven by interactions with other chemoreceptors and with CheW, CheV1, and CheA. These results suggest that TlpD can form an autonomous signaling unit. We further determined that TlpD mediates a repellent chemotaxis response to conditions that promote oxidative stress, including being in the presence of iron, hydrogen peroxide, paraquat, and metronidazole. Last, we found that all testedH. pyloristrains express TlpD, whereas other chemoreceptors were present to various degrees. Our data suggest a model in which TlpD coordinates a signaling complex that responds to oxidative stress and may allowH. pylorito avoid areas of the stomach with high concentrations of reactive oxygen species.IMPORTANCEHelicobacter pylorisenses its environment with proteins called chemoreceptors. Chemoreceptors integrate this sensory information to affect flagellum-based motility in a process called chemotaxis. Chemotaxis is employed during infection and presumably aidsH. pyloriin encountering and colonizing preferred niches. A cytoplasmic chemoreceptor named TlpD is particularly important in this process, and we report here that this chemoreceptor is able to operate independently of other chemoreceptors to organize a chemotaxis signaling complex and mediate a repellent response to oxidative stress conditions.H. pyloriencounters and must cope with oxidative stress during infection due to oxygen and reactive oxygen species produced by host cells. TlpD's repellent response may allow the bacteria to escape niches experiencing inflammation and elevated reactive oxygen species (ROS) production.


2012 ◽  
Vol 80 (11) ◽  
pp. 3892-3899 ◽  
Author(s):  
Azad Eshghi ◽  
Kristel Lourdault ◽  
Gerald L. Murray ◽  
Thanatchaporn Bartpho ◽  
Rasana W. Sermswan ◽  
...  

ABSTRACTPathogenicLeptospiraspp. are likely to encounter higher concentrations of reactive oxygen species induced by the host innate immune response. In this study, we characterizedLeptospira interroganscatalase (KatE), the only annotated catalase found within pathogenicLeptospiraspecies, by assessing its role in resistance to H2O2-induced oxidative stress and during infection in hamsters. PathogenicL. interrogansbacteria had a 50-fold-higher survival rate under H2O2-induced oxidative stress than did saprophyticL. biflexabacteria, and this was predominantly catalase dependent. We also characterized KatE, the only annotated catalase found within pathogenicLeptospiraspecies. Catalase assays performed with recombinant KatE confirmed specific catalase activity, while protein fractionation experiments localized KatE to the bacterial periplasmic space. The insertional inactivation ofkatEin pathogenicLeptospirabacteria drastically diminished leptospiral viability in the presence of extracellular H2O2and reduced virulence in an acute-infection model. Combined, these results suggest thatL. interrogansKatE confersin vivoresistance to reactive oxygen species induced by the host innate immune response.


mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Ju-Sim Kim ◽  
Lin Liu ◽  
Andrés Vázquez-Torres

ABSTRACT Our previous biochemical approaches showed that the oxidoreductase activity of the DnaJ protein facilitates the interaction of oxidized DksA with RNA polymerase. Investigations herein demonstrate that under biologically relevant conditions the DnaJ- and DksA-codependent activation of the stringent response in Salmonella undergoing oxidative stress involves the DnaK chaperone. Oxidation of DksA cysteine residues stimulates redox-based and holdase interactions with zinc-binding and C-terminal domains of DnaJ. Genetic and biochemical evidence indicates that His33 in the HPD motif in the J domain of DnaJ facilitates interactions of unfolded DksA with DnaK. A mutation in His33 in the J domain prevents the presentation of unfolded DksA to DnaK without limiting the oxidoreductase activity mapped to DnaJ’s zinc-2 site. Thr199 in the ATPase catalytic site of DnaK is required for the formation of the DksA/RNA polymerase complex. The DnaK/DnaJ/DksA complex enables the formation of an enzymatically active RNA polymerase holoenzyme that stimulates transcription of branched-chain amino acid and histidine metabolic genes in Salmonella exposed to reactive oxygen species. The DnaK/DnaJ chaperone protects Salmonella against the cytotoxicity associated with reactive oxygen species generated by the phagocyte NADPH oxidase in the innate host response. The antioxidant defenses associated with DnaK/DnaJ can in part be ascribed to the elicitation of the DksA-dependent stringent response and the protection this chaperone system provides against protein carbonylation in Salmonella undergoing oxidative stress. IMPORTANCE DksA was discovered 30 years ago in a screen for suppressors that reversed the thermosensitivity of Escherichia coli mutant strains deficient in DnaK/DnaJ, raising the possibility that this chaperone system may control DksA function. Since its serendipitous discovery, DksA has emerged as a key activator of the transcriptional program called the stringent response in Gram-negative bacteria experiencing diverse adverse conditions, including nutritional starvation or oxidative stress. DksA activates the stringent response through the allosteric control this regulatory protein exerts on the kinetics of RNA polymerase promoter open complexes. Recent investigations have shown that DksA overexpression protects dnaKJ mutant bacteria against heat shock indirectly via the ancestral chaperone polyphosphate, casting doubt on a possible complexation of DnaK, DnaJ, and DksA. Nonetheless, research presented herein demonstrates that the cochaperones DnaK and DnaJ enable DksA/RNA polymerase complex formation in response to oxidative stress.


2012 ◽  
Vol 80 (6) ◽  
pp. 2121-2132 ◽  
Author(s):  
Xiucai Xu ◽  
Tingting Liu ◽  
Aimei Zhang ◽  
Xingxing Huo ◽  
Qingli Luo ◽  
...  

ABSTRACTToxoplasma gondiiinfection in pregnant women may result in abortion or in fetal teratogenesis; however, the underlying mechanisms are still unclear. In this paper, based on a murine model, we showed that maternal infection with RH strainT. gondiitachyzoites induced elevated production of reactive oxygen species (ROS), local oxidative stress, and subsequent apoptosis of placental trophoblasts. PCR array analysis of 84 oxidative stress-related genes demonstrated that 27 genes were upregulated at least 2-fold and that 9 genes were downregulated at least 2-fold in theT. gondiiinfection group compared with levels in the control group. The expression of NADPH oxidase 1 (Nox1) and glutathione peroxidase 6 (Gpx6) increased significantly, about 25-fold. The levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) increased significantly withT. gondiiinfection, and levels of glutathione (GSH) decreased rapidly.T. gondiiinfection increased the early expression of endoplasmic reticulum stress (ERS) markers, followed by cleavage of caspase-12, activation of ASK1/JNK, and increased apoptosis of trophoblasts, bothin vivoandin vitro. The apoptosis of trophoblasts, the activation of caspase-12 and the ASK1/JNK pathway, and the production of peroxides were dramatically inhibited by pretreatment withN-acetylcysteine (NAC). The upregulation of Nox1 was contact dependent and preceded the increase in levels of ERS markers and the activation of the proapoptosis cascade. Thus, we concluded that apoptosis in placental trophoblasts was initiated predominantly by ROS-mediated ERS via activation of caspase-12, CHOP, and the JNK pathway in acuteT. gondiiinfection. Elevated ROS production is the central event inT. gondii-induced apoptosis of placental trophoblasts.


2018 ◽  
Vol 200 (7) ◽  
Author(s):  
Alisa P. Lehman ◽  
Sharon R. Long

ABSTRACTReactive oxygen species such as peroxides play an important role in plant development, cell wall maturation, and defense responses. During nodulation with the host plantMedicago sativa,Sinorhizobium meliloticells are exposed to H2O2in infection threads and developing nodules (R. Santos, D. Hérouart, S. Sigaud, D. Touati, and A. Puppo, Mol Plant Microbe Interact 14:86–89, 2001,https://doi.org/10.1094/MPMI.2001.14.1.86).S. meliloticells likely also experience oxidative stress, from both internal and external sources, during life in the soil. Here, we present microarray transcription data forS. melilotiwild-type cells compared to a mutant deficient in the key oxidative regulatory protein OxyR, each in response to H2O2treatment. Several alternative sigma factor genes are upregulated in the response to H2O2; the stress sigma generpoE2shows OxyR-dependent induction by H2O2, whilerpoH1expression is induced by H2O2irrespective of theoxyRgenotype. The activity of the RpoE2 sigma factor in turn causes increased expression of two more sigma factor genes,rpoE5andrpoH2. Strains with deletions ofrpoH1showed improved survival in H2O2as well as increased levels ofoxyRand total catalase expression. These results imply that ΔrpoH1strains are primed to deal with oxidative stress. This work presents a global view ofS. melilotigene expression changes, and of regulation of those changes, in response to H2O2.IMPORTANCELike all aerobic organisms, the symbiotic nitrogen-fixing bacteriumSinorhizobium melilotiexperiences oxidative stress throughout its complex life cycle. This report describes the global transcriptional changes thatS. melilotimakes in response to H2O2and the roles of the OxyR transcriptional regulator and the RpoH1 sigma factor in regulating those changes. By understanding the complex regulatory response ofS. melilotito oxidative stress, we may further understand the role that reactive oxygen species play as both stressors and potential signals during symbiosis.


2014 ◽  
Vol 197 (2) ◽  
pp. 277-285 ◽  
Author(s):  
Alistair Harrison ◽  
Beth D. Baker ◽  
Robert S. Munson

The Gram-negative commensal bacterium nontypeableHaemophilus influenzae(NTHI) can cause respiratory tract diseases that include otitis media, sinusitis, exacerbations of chronic obstructive pulmonary disease, and bronchitis. During colonization and infection, NTHI withstands oxidative stress generated by reactive oxygen species produced endogenously, by the host, and by other copathogens and flora. These reactive oxygen species include superoxide, hydrogen peroxide (H2O2), and hydroxyl radicals, whose killing is amplified by iron via the Fenton reaction. We previously identified genes that encode proteins with putative roles in protection of the NTHI isolate strain 86-028NP against oxidative stress. These include catalase (HktE), peroxiredoxin/glutaredoxin (PgdX), and a ferritin-like protein (Dps). Strains were generated with mutations inhktE,pgdX, anddps. ThehktEmutant and apgdX hktEdouble mutant were more sensitive than the parent to killing by H2O2. Conversely, thepgdXmutant was more resistant to H2O2due to increased catalase activity. Supporting the role of killing via the Fenton reaction, binding of iron by Dps significantly mitigated the effect of H2O2-mediated killing. NTHI thus utilizes several effectors to resist oxidative stress, and regulation of free iron is critical to this protection. These mechanisms will be important for successful colonization and infection by this opportunistic human pathogen.


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