scholarly journals Investigating the Roles of Listeria monocytogenes Peroxidases in Growth and Virulence

2021 ◽  
Author(s):  
Monica R. Cesinger ◽  
Nicole H. Schwardt ◽  
Cortney R. Halsey ◽  
Maureen K. Thomason ◽  
Michelle L. Reniere
Keyword(s):  
Reactive Oxygen Species ◽  
Immune System ◽  
Listeria Monocytogenes ◽  
Causative Agent ◽  
Foodborne Illness ◽  
Intracellular Pathogen ◽  
Host Immune System ◽  
Oxygen Species ◽  
Aerobic Growth ◽  
Content Type

Listeria monocytogenes is a facultative intracellular pathogen and the causative agent of the foodborne illness listeriosis. L. monocytogenes must contend with reactive oxygen species generated extracellularly during aerobic growth and intracellularly by the host immune system. However, the mechanisms by which L. monocytogenes defends against peroxide toxicity have not yet been defined.

scholarly journals The Dynll1-Cox4i1 Complex Regulates Intracellular Pathogen Clearance via Release of Mitochondrial Reactive Oxygen Species

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Jiangbei Yuan ◽  
Zihan Zheng ◽  
Liting Wang ◽  
Haiying Ran ◽  
Xiangyu Tang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Listeria Monocytogenes ◽  
Membrane Proteins ◽  
Defense Mechanisms ◽  
Reactive Oxygen ◽  
Cellular Membrane ◽  
Oxygen Species ◽  
Dynein Light Chain ◽  
Mitochondrial Reactive Oxygen Species ◽  
Content Type

ABSTRACT Cellular membrane proteins are a critical part of the host defense mechanisms against infection and intracellular survival of Listeria monocytogenes. The complex spatiotemporal regulation of bacterial infection by various membrane proteins has been challenging to study. Here, using mass spectrometry analyses, we depicted the dynamic expression landscape of membrane proteins upon L. monocytogenes infection in dendritic cells. We showed that Dynein light chain 1 (Dynll1) formed a persistent complex with the mitochondrial cytochrome oxidase Cox4i1, which is disturbed by pathogen insult. We discovered that the dissociation of the Dynll1-Cox4i1 complex is required for the release of mitochondrial reactive oxygen species and serves as a regulator of intracellular proliferation of Listeria monocytogenes. Our study shows that Dynll1 is an inhibitor of mitochondrial reactive oxygen species and can serve as a potential molecular drug target for antibacterial treatment.

scholarly journals Blue-Light Inhibition of Listeria monocytogenes Growth Is Mediated by Reactive Oxygen Species and Is Influenced by σBand the Blue-Light Sensor Lmo0799

2016 ◽  
Vol 82 (13) ◽  
pp. 4017-4027 ◽  
Author(s):  
Beth O'Donoghue ◽  
Kerrie NicAogáin ◽  
Claire Bennett ◽  
Alan Conneely ◽  
Teresa Tiensuu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Listeria Monocytogenes ◽  
Stress Response ◽  
Blue Light ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Content Type ◽  
General Stress Response ◽  
General Stress ◽  
Light Sensor

ABSTRACTListeria monocytogenessenses blue light via the flavin mononucleotide-containing sensory protein Lmo0799, leading to activation of the general stress response sigma factor SigB (σB). In this study, we investigated the physiological response of this foodborne pathogen to blue light. We show that blue light (460 to 470 nm) doses of 1.5 to 2 mW cm−2cause inhibition of growth on agar-based and liquid culture media. The inhibitory effects are dependent on cell density, with reduced effects evident when high cell numbers are present. The addition of 20 mM dimethylthiourea, a scavenger of reactive oxygen species, or catalase to the medium reverses the inhibitory effects of blue light, suggesting that growth inhibition is mediated by the formation of reactive oxygen species. A mutant strain lacking σB(ΔsigB) was found to be less inhibited by blue light than the wild type, likely indicating the energetic cost of deploying the general stress response. When a lethal dose of light (8 mW cm−2) was applied to cells, the ΔsigBmutant displayed a marked increase in sensitivity to light compared to the wild type. To investigate the role of the blue-light sensor Lmo0799, mutants were constructed that either had a deletion of the gene (Δlmo0799) or alteration in a conserved cysteine residue at position 56, which is predicted to play a pivotal role in the photocycle of the protein (lmo0799C56A). Both mutants displayed phenotypes similar to the ΔsigBmutant in the presence of blue light, providing genetic evidence that residue 56 is critical for light sensing inL. monocytogenes. Taken together, these results demonstrate thatL. monocytogenesis inhibited by blue light in a manner that depends on reactive oxygen species, and they demonstrate clear light-dependent phenotypes associated with σBand the blue-light sensor Lmo0799.IMPORTANCEListeria monocytogenesis a bacterial foodborne pathogen that can cause life-threatening infections in humans. It is known to be able to sense and respond to visible light. In this study, we examine the effects of blue light on the growth and survival of this pathogen. We show that growth can be inhibited at comparatively low doses of blue light, and that at higher doses,L. monocytogenescells are killed. We present evidence suggesting that blue light inhibits this organism by causing the production of reactive oxygen species, such as hydrogen peroxide. We help clarify the mechanism of light sensing by constructing a “blind” version of the blue-light sensor protein. Finally, we show that activation of the general stress response by light has a negative effect on growth, probably because cellular resources are diverted into protective mechanisms rather than growth.

scholarly journals Ubiquitination of Listeria Virulence Factor InlC Contributes to the Host Response to Infection

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Edith Gouin ◽  
Damien Balestrino ◽  
Orhan Rasid ◽  
Marie-Anne Nahori ◽  
Véronique Villiers ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Immune Response ◽  
Listeria Monocytogenes ◽  
Host Response ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Pathogenic Potential ◽  
Content Type ◽  
Species Production

ABSTRACT Listeria monocytogenes is a pathogenic bacterium causing potentially fatal foodborne infections in humans and animals. While the mechanisms used by Listeria to manipulate its host have been thoroughly characterized, how the host controls bacterial virulence factors remains to be extensively deciphered. Here, we found that the secreted Listeria virulence protein InlC is monoubiquitinated by the host cell machinery on K224, restricting infection. We show that the ubiquitinated form of InlC interacts with the intracellular alarmin S100A9, resulting in its stabilization and in increased reactive oxygen species production by neutrophils in infected mice. Collectively, our results suggest that posttranslational modification of InlC exacerbates the host response upon Listeria infection. IMPORTANCE The pathogenic potential of Listeria monocytogenes relies on the production of an arsenal of virulence determinants that have been extensively characterized, including surface and secreted proteins of the internalin family. We have previously shown that the Listeria secreted internalin InlC interacts with IκB kinase α to interfere with the host immune response (E. Gouin, M. Adib-Conquy, D. Balestrino, M.-A. Nahori, et al., Proc Natl Acad Sci USA, 107:17333–17338, 2010, https://doi.org/10.1073/pnas.1007765107). In the present work, we report that InlC is monoubiquitinated on K224 upon infection of cells and provide evidence that ubiquitinated InlC interacts with and stabilizes the alarmin S100A9, which is a critical regulator of the immune response and inflammatory processes. Additionally, we show that ubiquitination of InlC causes an increase in reactive oxygen species production by neutrophils in mice and restricts Listeria infection. These findings are the first to identify a posttranscriptional modification of an internalin contributing to host defense.

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
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Dental Caries ◽  
Signaling Pathway ◽  
Streptococcus Mutans ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Oral Biofilm ◽  
Genetic Competence ◽  
Content Type

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.

scholarly journals Sources of ROS Species an Its Harmful and Benefical Effects on Human Health

2021 ◽  
Author(s):  
Sidra Munir
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Antioxidant Enzymes ◽  
Immune System ◽  
Cardiovascular Diseases ◽  
Partial Oxidation ◽  
Human Body ◽  
Therapeutic Potential ◽  
Oxygen Species ◽  
Essential Function

When the antioxidants in our immune system cannot neutralize or convert Reactive oxygen species into safe molecules at the rate at which it is produced then this imbalance is termed as “oxidative stress”. It is related with a wide array of diseases that includes cancer, diabetes, cardiovascular diseases, hypertension etc. These ROS species however are utmost essential for the proper functioning of human body which are produced as a consequence of partial oxidation of cellular metabolism performing essential functions such as protein phosphorylation, activation of several transcriptional factors, apoptosis, immunity, and differentiation. The sources by which these are produced can be broadly classified are intrinsic and extrinsic sources. There are variety of natural antioxidant enzymes of human body that combat against this oxidative stress. The extrinsic sources of ROS include the use of natural plants, extracted flavonoids and vitamins. In this review we will briefly explain how the sources of ROS, its essential function in human body, its elevation and associated damage to organs and effect on various diseases, and a hope of finding a way of how this oxidative stress can be exploited for therapeutic potential.

scholarly journals Fengycins, Cyclic Lipopeptides from MarineBacillus subtilisStrains, Kill the Plant-Pathogenic FungusMagnaporthe griseaby Inducing Reactive Oxygen Species Production and Chromatin Condensation

2018 ◽  
Vol 84 (18) ◽  
Author(s):  
Linlin Zhang ◽  
Chaomin Sun
Keyword(s):  
Mass Spectrometry ◽  
Reactive Oxygen Species ◽  
Biological Control ◽  
Bacillus Subtilis ◽  
Rice Blast ◽  
Marine Bacterium ◽  
Magnaporthe Grisea ◽  
Chromatin Condensation ◽  
Oxygen Species ◽  
Content Type

ABSTRACTRice blast caused by the phytopathogenMagnaporthe griseaposes a serious threat to global food security and is difficult to control.Bacillusspecies have been extensively explored for the biological control of many fungal diseases. In the present study, the marine bacteriumBacillus subtilisBS155 showed a strong antifungal activity againstM. grisea. The active metabolites were isolated and identified as cyclic lipopeptides (CLPs) of the fengycin family, named fengycin BS155, by the combination of high-performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS). Analyses using scanning and transmission electron microscopy revealed that fengycin BS155 caused morphological changes in the plasma membrane and cell wall ofM. griseahyphae. Using comparative proteomic and biochemical assays, fengycin BS155 was demonstrated to reduce the mitochondrial membrane potential (MMP), induce bursts of reactive oxygen species (ROS), and downregulate the expression level of ROS-scavenging enzymes. Simultaneously, fengycin BS155 caused chromatin condensation in fungal hyphal cells, which led to the upregulation of DNA repair-related protein expression and the cleavage of poly(ADP-ribose) polymerase (PARP). Altogether, our results indicate that fengycin BS155 acts by inducing membrane damage and dysfunction of organelles, disrupting MMP, oxidative stress, and chromatin condensation, resulting inM. griseahyphal cell death. Therefore, fengycin BS155 and its parent bacterium are very promising candidates for the biological control ofM. griseaand the associated rice blast and should be further investigated as such.IMPORTANCERice (Oryza sativaL.) is the most important crop and a primary food source for more than half of the world's population. Notably, scientists in China have developed several types of rice that can be grown in seawater, avoiding the use of precious freshwater resources and potentially creating enough food for 200 million people. The plant-affecting fungusMagnaporthe griseais the causal agent of rice blast disease, and biological rather than chemical control of this threatening disease is highly desirable. In this work, we discovered fengycin BS155, a cyclic lipopeptide material produced by the marine bacteriumBacillus subtilisBS155, which showed strong activity againstM. grisea. Our results elucidate the mechanism of fengycin BS155-mediatedM. griseagrowth inhibition and highlight the potential ofB. subtilisBS155 as a biocontrol agent againstM. griseain rice cultivation under both fresh- and saltwater conditions.

scholarly journals Staphylococcal DNA Repair Is Required for Infection

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Kam Pou Ha ◽  
Rebecca S. Clarke ◽  
Gyu-Lee Kim ◽  
Jane L. Brittan ◽  
Jessica E. Rowley ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Staphylococcus Aureus ◽  
Human Blood ◽  
Immune Cells ◽  
Double Strand Breaks ◽  
Oxygen Species ◽  
Dna Double Strand Breaks ◽  
Gram Positive ◽  
Content Type ◽  
Strand Breaks

ABSTRACT To cause infection, Staphylococcus aureus must withstand damage caused by host immune defenses. However, the mechanisms by which staphylococcal DNA is damaged and repaired during infection are poorly understood. Using a panel of transposon mutants, we identified the rexBA operon as being important for the survival of Staphylococcus aureus in whole human blood. Mutants lacking rexB were also attenuated for virulence in murine models of both systemic and skin infections. We then demonstrated that RexAB is a member of the AddAB family of helicase/nuclease complexes responsible for initiating the repair of DNA double-strand breaks. Using a fluorescent reporter system, we were able to show that neutrophils cause staphylococcal DNA double-strand breaks through reactive oxygen species (ROS) generated by the respiratory burst, which are repaired by RexAB, leading to the induction of the mutagenic SOS response. We found that RexAB homologues in Enterococcus faecalis and Streptococcus gordonii also promoted the survival of these pathogens in human blood, suggesting that DNA double-strand break repair is required for Gram-positive bacteria to survive in host tissues. Together, these data demonstrate that DNA is a target of host immune cells, leading to double-strand breaks, and that the repair of this damage by an AddAB-family enzyme enables the survival of Gram-positive pathogens during infection. IMPORTANCE To cause infection, bacteria must survive attack by the host immune system. For many bacteria, including the major human pathogen Staphylococcus aureus, the greatest threat is posed by neutrophils. These immune cells ingest the invading organisms and try to kill them with a cocktail of chemicals that includes reactive oxygen species (ROS). The ability of S. aureus to survive this attack is crucial for the progression of infection. However, it was not clear how the ROS damaged S. aureus and how the bacterium repaired this damage. In this work, we show that ROS cause breaks in the staphylococcal DNA, which must be repaired by a two-protein complex known as RexAB; otherwise, the bacterium is killed, and it cannot sustain infection. This provides information on the type of damage that neutrophils cause S. aureus and the mechanism by which this damage is repaired, enabling infection.

scholarly journals Ascorbate-Dependent Peroxidase (APX) from Leishmania amazonensis Is a Reactive Oxygen Species-Induced Essential Enzyme That Regulates Virulence

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Lucia Xiang ◽  
Maria Fernanda Laranjeira-Silva ◽  
Fernando Y. Maeda ◽  
Jason Hauzel ◽  
Norma W. Andrews ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Macrophage Infection ◽  
Cutaneous Lesions ◽  
Signaling Mechanism ◽  
Content Type ◽  
Temporal Regulation ◽  
Metacyclic Promastigotes

ABSTRACT The molecular mechanisms underlying biological differences between two Leishmania species that cause cutaneous disease, L. major and L. amazonensis, are poorly understood. In L. amazonensis, reactive oxygen species (ROS) signaling drives differentiation of nonvirulent promastigotes into forms capable of infecting host macrophages. Tight spatial and temporal regulation of H2O2 is key to this signaling mechanism, suggesting a role for ascorbate-dependent peroxidase (APX), which degrades mitochondrial H2O2. Earlier studies showed that APX-null L. major parasites are viable, accumulate higher levels of H2O2, generate a greater yield of infective metacyclic promastigotes, and have increased virulence. In contrast, we found that in L. amazonensis, the ROS-inducible APX is essential for survival of all life cycle stages. APX-null promastigotes could not be generated, and parasites carrying a single APX allele were impaired in their ability to infect macrophages and induce cutaneous lesions in mice. Similar to what was reported for L. major, APX depletion in L. amazonensis enhanced differentiation of metacyclic promastigotes and amastigotes, but the parasites failed to replicate after infecting macrophages. APX expression restored APX single-knockout infectivity, while expression of catalytically inactive APX drastically reduced virulence. APX overexpression in wild-type promastigotes reduced metacyclogenesis, but enhanced intracellular survival following macrophage infection or inoculation into mice. Collectively, our data support a role for APX-regulated mitochondrial H2O2 in promoting differentiation of virulent forms in both L. major and L. amazonensis. Our results also uncover a unique requirement for APX-mediated control of ROS levels for survival and successful intracellular replication of L. amazonensis.

scholarly journals Investigation of bacterial resistance to the immune system response: Cepacian depolymerisation by reactive oxygen species

2012 ◽  
Vol 18 (4) ◽  
pp. 661-671 ◽  
Author(s):  
Bruno Cuzzi ◽  
Paola Cescutti ◽  
Linda Furlanis ◽  
Cristina Lagatolla ◽  
Luisa Sturiale ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Immune System ◽  
Bacterial Resistance ◽  
Reactive Oxygen ◽  
System Response ◽  
Oxygen Species ◽  
Immune System Response

scholarly journals Selected Immunological Mediators and Cervical Microbial Signatures in Women with Chlamydia trachomatis Infection

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Simone Filardo ◽  
Marisa Di Pietro ◽  
Giulia Tranquilli ◽  
Maria Agnese Latino ◽  
Nadia Recine ◽  
...  
Keyword(s):  
Immune System ◽  
Chlamydia Trachomatis ◽  
Host Immune System ◽  
Complex Interplay ◽  
Content Type ◽  
Immune Mediators ◽  
Potential Biomarker ◽  
Ifn Γ ◽  
Low Levels ◽  
Female Genital

ABSTRACT In the female genital ecosystem, the complex interplay between the host immune system and the resident microflora protects against urogenital pathogens, like Chlamydia trachomatis. C. trachomatis is responsible for urethritis and cervicitis; however, most chlamydial infections are asymptomatic and, thus, not treated, potentially leading to severe reproductive sequelae. Here we investigated the interaction between the levels of selected immune mediators and the community state types of the cervical microbiota in C. trachomatis-infected women. Cervical samples from 42 C. trachomatis-positive women and 103 matched healthy controls were analyzed through the metagenomic analysis of the hypervariable region v4 of the 16S rRNA gene and the determination of lactoferrin, interleukin 1α (IL-1α), IL-6, alpha interferon (IFN-α), IFN-β, and IFN-γ by ELISA. Overall, C. trachomatis infection was significantly associated with a microbiota dominated by anaerobic bacteria (P = 0.000002). In addition, a network of Gardnerella vaginalis, Prevotella amnii, Prevotella buccalis, Prevotella timonensis, Aerococcus christensenii, and Variovorax guangxiensis has been identified as a potential biomarker of C. trachomatis infection through multiple statistical approaches. Again, chlamydial infection was significantly correlated with an increased production of lactoferrin, IL-6, IL-1α, IFN-α, and IFN-β (P < 0.05), whereas very low levels of IFN-γ were observed in C. trachomatis-infected women, levels similar to those detected in healthy women. Our findings show a distinctive signature of C. trachomatis genital infection, characterized by a specific bacterial network, constituted by anaerobes, as well as by increased levels of lactoferrin and proinflammatory cytokines (IL-1α, IL-6, IFN-α, and IFN-β), accompanied by low levels of IFN-γ. IMPORTANCE To our knowledge, this is the first study that investigated the association of C. trachomatis with the cervical levels of lactoferrin and selected inflammatory mediators and their correlation with the different community state types characterizing the female genital ecosystem. C. trachomatis, known as the leading cause of bacterial sexually transmitted diseases, continues to be an important public health problem worldwide for its increasing incidence and the risk of developing severe reproductive sequelae, like pelvic inflammatory disease and infertility. Specifically, C. trachomatis tend to persist in the female genital tract, leading to a chronic inflammatory state characterized by increased production of immune mediators responsible for tissue damage. Therefore, our study may help to broaden the knowledge on the complex interplay between the female genital microbiota and the host immune system in response to C. trachomatis infection.

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