scholarly journals Candida albicans infection disturbs the redox homeostasis system and induces reactive oxygen species accumulation for epithelial cell death

2019 ◽  
Vol 20 (4) ◽  
Author(s):  
Tongtong Ren ◽  
Hangqi Zhu ◽  
Lei Tian ◽  
Qilin Yu ◽  
Mingchun Li
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Candida Albicans ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Tissue Damage ◽  
Redox Homeostasis ◽  
Oxygen Species ◽  
Ros Accumulation ◽  
Epithelial Cell Death

ABSTRACT Candida albicans is a common pathogenic fungus with high mortality in immunocompromised patients. However, the mechanism by which C. albicans invades host epithelial cells and causes serious tissue damage remains to be further investigated. In this study, we established the C. albicans–293T renal epithelial cell interaction model to investigate the mechanism of epithelial infection by this pathogen. It was found that C. albicans infection causes severe cell death and reactive oxygen species (ROS) accumulation in epithelial cells. Further investigations revealed that C. albicans infection might up-regulate expression of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX), inhibit the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and suppress the p38–Nrf2–heme oxygenase-1 (HO-1) pathway which plays an important role in the elimination of intracellular ROS. Furthermore, epithelial cell death caused by the fungal infection could be strikingly alleviated by addition of the antioxidant agent glutathione, indicating the critical role of ROS accumulation in cell death caused by the fungus. This study revealed that disturbance of the redox homeostasis system and ROS accumulation in epithelial cells is involved in cell death caused by C. albicans infection, which sheds light on the application of antioxidants in the suppression of tissue damage caused by fungal infection.

scholarly journals Post-stress bacterial cell death mediated by reactive oxygen species

2019 ◽  
Vol 116 (20) ◽  
pp. 10064-10071 ◽  
Author(s):  
Yuzhi Hong ◽  
Jie Zeng ◽  
Xiuhong Wang ◽  
Karl Drlica ◽  
Xilin Zhao
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Bacterial Resistance ◽  
Reactive Oxygen ◽  
Temperature Sensitive ◽  
Oxygen Species ◽  
Stress Genes ◽  
Primary Stress ◽  
Bacterial Cell Death ◽  
Ros Accumulation

Antimicrobial efficacy, which is central to many aspects of medicine, is being rapidly eroded by bacterial resistance. Since new resistance can be induced by antimicrobial action, highly lethal agents that rapidly reduce bacterial burden during infection should help restrict the emergence of resistance. To improve lethal activity, recent work has focused on toxic reactive oxygen species (ROS) as part of the bactericidal activity of diverse antimicrobials. We report that whenEscherichia coliwas subjected to antimicrobial stress and the stressor was subsequently removed, both ROS accumulation and cell death continued to occur. Blocking ROS accumulation by exogenous mitigating agents slowed or inhibited poststressor death. Similar results were obtained with a temperature-sensitive mutational inhibition of DNA replication. Thus, bacteria exposed to lethal stressors may not die during treatment, as has long been thought; instead, death can occur after plating on drug-free agar due to poststress ROS-mediated toxicity. Examples are described in which (i) primary stress-mediated damage was insufficient to kill bacteria due to repair; (ii) ROS overcame repair (i.e., protection from anti-ROS agents was reduced by repair deficiencies); and (iii) killing was reduced by anti-oxidative stress genes acting before stress exposure. Enzymatic suppression of poststress ROS-mediated lethality by exogenous catalase supports a causal rather than a coincidental role for ROS in stress-mediated lethality, thereby countering challenges to ROS involvement in antimicrobial killing. We conclude that for a variety of stressors, lethal action derives, at least in part, from stimulation of a self-amplifying accumulation of ROS that overwhelms the repair of primary damage.

scholarly journals Dimethyl Sulfoxide Protects Escherichia coli from Rapid Antimicrobial-Mediated Killing

2016 ◽  
Vol 60 (8) ◽  
pp. 5054-5058 ◽  
Author(s):  
Hongfei Mi ◽  
Dai Wang ◽  
Yunxin Xue ◽  
Zhi Zhang ◽  
Jianjun Niu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Dimethyl Sulfoxide ◽  
Oxygen Species ◽  
Content Type ◽  
Antimicrobial Studies ◽  
Ros Accumulation ◽  
Short Time

ABSTRACTThe contribution of reactive oxygen species (ROS) to antimicrobial lethality was examined by treatingEscherichia coliwith dimethyl sulfoxide (DMSO), an antioxidant solvent frequently used in antimicrobial studies. DMSO inhibited killing by ampicillin, kanamycin, and two quinolones and had little effect on MICs. DMSO-mediated protection correlated with decreased ROS accumulation and provided evidence for ROS-mediated programmed cell death. These data support the contribution of ROS to antimicrobial lethality and suggest caution when using DMSO-dissolved antimicrobials for short-time killing assays.

Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide

2005 ◽  
Vol 288 (2) ◽  
pp. L342-L349 ◽  
Author(s):  
Hiroshi Kida ◽  
Mitsuhiro Yoshida ◽  
Shigenori Hoshino ◽  
Koji Inoue ◽  
Yukihiro Yano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Lung Fibroblasts ◽  
Alveolar Epithelial ◽  
Epithelial Cell Death

The goal of this study was to examine whether IL-6 could directly protect lung resident cells, especially alveolar epithelial cells, from reactive oxygen species (ROS)-induced cell death. ROS induced IL-6 gene expression in organotypic lung slices of wild-type (WT) mice. ROS also induced IL-6 gene expression in mouse primary lung fibroblasts, dose dependently. The organotypic lung slices of WT were more resistant to ROS-induced DNA fragmentation than those of IL-6-deficient (IL-6−/−) mice. WT resistance against ROS was abrogated by treatment with anti-IL-6 antibody. TdT-mediated dUTP nick end labeling stain and electron microscopy revealed that DNA fragmented cells in the IL-6−/− slice included alveolar epithelial cells and endothelial cells. In vitro studies demonstrated that IL-6 reduced ROS-induced A549 alveolar epithelial cell death. Together, these data suggest that IL-6 played an antioxidant role in the lung by protecting lung resident cells, especially alveolar epithelial cells, from ROS-induced cell death.

scholarly journals Synthetic bottom-up approach reveals the complex interplay ofShigellaeffectors in regulation of epithelial cell death

2018 ◽  
Vol 115 (25) ◽  
pp. 6452-6457 ◽  
Author(s):  
Xiangyu Mou ◽  
Skye Souter ◽  
Juan Du ◽  
Analise Z. Reeves ◽  
Cammie F. Lesser
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Host Cells ◽  
Bottom Up ◽  
Type Iii Effectors ◽  
Type Iii ◽  
Bacterial Replication ◽  
Almost All ◽  
Epithelial Cell Death

Over the course of an infection, many Gram-negative bacterial pathogens use complex nanomachines to directly inject tens to hundreds of proteins (effectors) into the cytosol of infected host cells. These effectors rewire processes to promote bacterial replication and spread. The roles of effectors in pathogenesis have traditionally been investigated by screening for phenotypes associated with their absence, a top-down approach that can be limited, as effectors often act in a functionally redundant or additive manner. Here we describe a syntheticEscherichia coli-based bottom-up platform to conduct gain-of-function screens for roles of individualShigellaeffectors in pathogenesis. As proof of concept, we screened forShigellaeffectors that limit cell death induced on cytosolic entry of bacteria into epithelial cells. Using this platform, in addition to OspC3, an effector known to inhibit cell death via pyroptosis, we have identified OspD2 and IpaH1.4 as cell death inhibitors. In contrast to almost all type III effectors, OspD2 does not target a host cell process, but rather regulates the activity of theShigellatype III secretion apparatus limiting the cytosolic delivery (translocation) of effectors during an infection. Remarkably, by limiting the translocation of a single effector, VirA, OspD2 controls the timing of epithelial cell death via calpain-mediated necrosis. Together, these studies provide insight into the intricate manner by whichShigellaeffectors interact to establish a productive intracytoplasmic replication niche before the death of infected epithelial cells.

scholarly journals Reactive oxygen species induced by Streptococcus pyogenes invasion trigger apoptotic cell death in infected epithelial cells

2010 ◽  
Vol 12 (6) ◽  
pp. 814-830 ◽  
Author(s):  
Chihiro Aikawa ◽  
Takashi Nozawa ◽  
Fumito Maruyama ◽  
Kohei Tsumoto ◽  
Shigeyuki Hamada ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Epithelial Cells ◽  
Streptococcus Pyogenes ◽  
Apoptotic Cell ◽  
Reactive Oxygen ◽  
Apoptotic Cell Death ◽  
Oxygen Species

scholarly journals Impact of vaginal douching products on vaginal Lactobacillus, Escherichia coli and epithelial immune responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Helai Hesham ◽  
Alissa J. Mitchell ◽  
Agnes Bergerat ◽  
Kristin Hung ◽  
Caroline M. Mitchell
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Immune Responses ◽  
E Coli ◽  
Vaginal Douching ◽  
Vaginal Epithelial Cells ◽  
Epithelial Disruption ◽  
Epithelial Cell Death

AbstractWe compared the effect of commercial vaginal douching products on Lactobacillus crispatus, L. jensenii, L. gasseri, L. iners, E. coli, and immortalized vaginal epithelial cells (VK2). All studied douching products (vinegar, iodine and baking soda based) induced epithelial cell death, and all inhibited growth of E. coli. Co-culture of vaginal epithelial cells with any of the lactobacilli immediately following exposure to douching products resulted in a trend to less human cell death. However, co-culture of epithelial cells with L. iners was associated with higher production of IL6 and IL8, and lower IL1RA regardless of presence or type of douching solution. Co-culture with L. crispatus or L. jensenii decreased IL6 production in the absence of douches, but increased IL6 production after exposure to vinegar. Douching products may be associated with epithelial disruption and inflammation, and may reduce the anti-inflammatory effects of beneficial lactobacilli.

Apigenin drives the production of reactive oxygen species and initiates a mitochondrial mediated cell death pathway in prostate epithelial cells

The Prostate ◽  
2005 ◽  
Vol 63 (2) ◽  
pp. 131-142 ◽  
Author(s):  
Colm Morrissey ◽  
Amanda O'Neill ◽  
Barbara Spengler ◽  
Volker Christoffel ◽  
John M. Fitzpatrick ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Epithelial Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cell Death Pathway ◽  
Prostate Epithelial Cells

scholarly journals N-Acetylglucosamine-Induced Cell Death in Candida albicans and Its Implications for Adaptive Mechanisms of Nutrient Sensing in Yeasts

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Han Du ◽  
Guobo Guan ◽  
Xiaoling Li ◽  
Megha Gulati ◽  
Li Tao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Candida Albicans ◽  
Fungal Pathogen ◽  
Reactive Oxygen ◽  
Nutrient Sensing ◽  
Oxygen Species ◽  
Gi Tract ◽  
Content Type ◽  
Cell Death Pathway

ABSTRACT Single-celled organisms have different strategies to sense and utilize nutrients in their ever-changing environments. The opportunistic fungal pathogen Candida albicans is a common member of the human microbiota, especially that of the gastrointestinal (GI) tract. An important question concerns how C. albicans gained a competitive advantage over other microbes to become a successful commensal and opportunistic pathogen. Here, we report that C. albicans uses N-acetylglucosamine (GlcNAc), an abundant carbon source present in the GI tract, as a signal for nutrient availability. When placed in water, C. albicans cells normally enter the G0 phase and remain viable for weeks. However, they quickly lose viability when cultured in water containing only GlcNAc. We term this phenomenon GlcNAc-induced cell death (GICD). GlcNAc triggers the upregulation of ribosomal biogenesis genes, alterations of mitochondrial metabolism, and the accumulation of reactive oxygen species (ROS), followed by rapid cell death via both apoptotic and necrotic mechanisms. Multiple pathways, including the conserved cyclic AMP (cAMP) signaling and GlcNAc catabolic pathways, are involved in GICD. GlcNAc acts as a signaling molecule to regulate multiple cellular programs in a coordinated manner and therefore maximizes the efficiency of nutrient use. This adaptive behavior allows C. albicans’ more efficient colonization of the gut. IMPORTANCE The ability to rapidly and appropriately respond to nutrients in the environment is crucial to free-living microorganisms. To maximize the use of available nutrients, microorganisms often use a limiting nutritional component as a signal to coordinate multiple biological processes. The human fungal pathogen Candida albicans uses N-acetylglucosamine (GlcNAc) as a signal for the availability of external nutrient resources. GlcNAc induces rapid cell death in C. albicans due to the constitutive activation of oxidative metabolism and accumulation of reactive oxygen species (ROS), and multiple pathways are involved in its regulation. This study sheds light on the mechanisms of niche specialization of pathogenic fungi and raises the possibility that this cell death pathway could be an unexplored therapeutic target.

scholarly journals Antimicrobial peptide AMP-17 exerts anti-Candida albicans effects through ROS-mediated apoptosis and necrosis

2020 ◽  
Author(s):  
Huiling Ma ◽  
Longbing Yang ◽  
Zhuqing Tian ◽  
Lijuan Zhu ◽  
JiangFan Xiu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Candida Albicans ◽  
Membrane Potential ◽  
Antimicrobial Peptide ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Oxygen Species ◽  
Ros Accumulation ◽  
Apoptosis And Necrosis

Abstract Background: New anti-candida albicans drugs need to be developed due to the emergence of drug-resistant cases in recent years. AMP-17 (Musca. domestica antimicrobial pepitide-17) is an antimicrobial peptide from M. domestica, which inhibits many fungal pathogens including Candida albicans (C. albicans) effectively. In this article, we discuss the potential mechanism of AMP-17 against C. albicans from the perspective of affecting its cell internal structure.Methods: After AMP-17 treatment, we examined the ultrastructure of C. albicans by transmission electron microscopy (TEM) and detected the cell cycle using flow cytometry. Fluorescent probes were used to examine the reactive oxygen species (ROS) accumulation in C. albicans cells and to analyze the correlation between ROS accumulation and C. albicans cell necrosis. The JC-1 kit was used to measure the effect of AMP-17 on the mitochondrial membrane potential (MMP) of C. albicans cells. AMP-17-induced apoptosis and necrosis was investigated using an Annexin V-FITC apoptosis detection kit.Results: Morphological observations showed that the shape of C. albicans treated with AMP-17 was irregular, and vacuoles were found in the cytoplasmic region. The treatment of C. albicans with AMP-17 resulted in the elevation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (MMP), and changes in cell cycle, which promoted apoptosis and necrosis of C. albicans cells. The level of apoptosis increased in a dose-dependent manner after AMP-17 treatment.Conclusions: AMP-17 inhibited the growth and proliferation of C. albicans cells by altering the cell cycle of C. albicans. In addition, AMP-17 stimulated mitochondria to produce excess ROS for anti-stress, but the excess ROS damages the function of mitochondria in return and results in the alteration of MMP. All of these ultimately contributes to the death of C. albicans.

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