scholarly journals Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection

mBio ◽  
2021 ◽  
Author(s):  
Victor Brantl ◽  
Jana M. Boysen ◽  
Annie Yap ◽  
Evgeny Golubtsov ◽  
Dominik Ruf ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Aspergillus Fumigatus ◽  
Virulence Factor ◽  
Vaccine Candidate ◽  
Reactive Oxygen ◽  
Iron Limitation ◽  
Oxygen Species ◽  
Content Type ◽  
Ros Scavenger ◽  
Fungal Allergen

Asp f3 is one of the most abundant proteins in the pathogenic mold Aspergillus fumigatus . It has an enigmatic multifaceted role as a fungal allergen, virulence factor, reactive oxygen species (ROS) scavenger, and vaccine candidate.

scholarly journals The Small GTPase RacA Mediates Intracellular Reactive Oxygen Species Production, Polarized Growth, and Virulence in the Human Fungal Pathogen Aspergillus fumigatus

2010 ◽  
Vol 10 (2) ◽  
pp. 174-186 ◽  
Author(s):  
Haiyan Li ◽  
Bridget M. Barker ◽  
Nora Grahl ◽  
Srisombat Puttikamonkul ◽  
Jeremey D. Bell ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Aspergillus Fumigatus ◽  
Invasive Pulmonary Aspergillosis ◽  
Reactive Oxygen ◽  
Small Gtpase ◽  
Oxygen Species ◽  
Wild Type ◽  
Content Type ◽  
Diphenylene Iodonium

ABSTRACTAspergillus fumigatusis the predominant mold pathogen in immunocompromised patients. In this study, we present the first characterization of the small GTPase RacA inA. fumigatus. To gain insight into the function ofracAin the growth and pathogenesis ofA. fumigatus, we constructed a strain that lacks a functionalracAgene. The ΔracAstrain showed significant morphological defects, including a reduced growth rate and abnormal conidiogenesis on glucose minimal medium. In the ΔracAstrain, apical dominance in the leading hyphae is lost and, instead, multiple axes of polarity emerge. Intriguingly, superoxide production at the hyphal tips was reduced by 25% in the ΔracAstrain. Treatment of wild-type hyphae with diphenylene iodonium, an inhibitor of NADPH oxidase, resulted in phenotypes similar to that of the ΔracAstrain. These data suggest that ΔracAstrain phenotypes may be due to a reduction or alteration in the production of reactive oxygen species. Most surprisingly, despite these developmental and growth abnormalities, the ΔracAstrain retained at least wild-type virulence in both an insect model and two immunologically distinct murine models of invasive pulmonary aspergillosis. These results demonstrate thatin vitrogrowth phenotypes do not always correlate within vivovirulence and raise intriguing questions about the role of RacA inAspergillusvirulence.

scholarly journals Induction of Mitochondrial Reactive Oxygen Species Production by Itraconazole, Terbinafine, and Amphotericin B as a Mode of Action against Aspergillus fumigatus

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Elena Shekhova ◽  
Olaf Kniemeyer ◽  
Axel A. Brakhage
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Complex I ◽  
Reactive Oxygen ◽  
Antifungal Compounds ◽  
Ros Production ◽  
Oxygen Species ◽  
Content Type

ABSTRACT Drug resistance in fungal pathogens is of incredible importance to global health, yet the mechanisms of drug action remain only loosely defined. Antifungal compounds have been shown to trigger the intracellular accumulation of reactive oxygen species (ROS) in human-pathogenic yeasts, but the source of those ROS remained unknown. In the present study, we examined the role of endogenous ROS for the antifungal activity of the three different antifungal substances itraconazole, terbinafine, and amphotericin B, which all target the fungal cell membrane. All three antifungals had an impact on fungal redox homeostasis by causing increased intracellular ROS production. Interestingly, the elevated ROS levels induced by antifungals were abolished by inhibition of the mitochondrial respiratory complex I with rotenone. Further, evaluation of lipid peroxidation using the thiobarbituric acid assay revealed that rotenone pretreatment decreased ROS-induced lipid peroxidation during incubation of Aspergillus fumigatus with itraconazole and terbinafine. By applying the mitochondrion-specific lipid peroxidation probe MitoPerOx, we also confirmed that ROS are induced in mitochondria and subsequently cause significant oxidation of mitochondrial membrane in the presence of terbinafine and amphotericin B. To summarize, our study suggests that the induction of ROS production contributes to the ability of antifungal compounds to inhibit fungal growth. Moreover, mitochondrial complex I is the main source of deleterious ROS production in A. fumigatus challenged with antifungal compounds.

scholarly journals An example of molecular co-evolution: Reactive oxygen species (ROS) and ROS scavenger levels in Schistosoma mansoni/Biomphalaria glabrata interactions

2011 ◽  
Vol 41 (7) ◽  
pp. 721-730 ◽  
Author(s):  
Yves Moné ◽  
Anne-Cécile Ribou ◽  
Céline Cosseau ◽  
David Duval ◽  
André Théron ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Schistosoma Mansoni ◽  
Reactive Oxygen ◽  
Biomphalaria Glabrata ◽  
Oxygen Species ◽  
Ros Scavenger

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 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 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.

Fe-S Cluster Biosynthesis Controls Uptake of Aminoglycosides in a ROS-Less Death Pathway

Science ◽  
2013 ◽  
Vol 340 (6140) ◽  
pp. 1583-1587 ◽  
Author(s):  
Benjamin Ezraty ◽  
Alexandra Vergnes ◽  
Manuel Banzhaf ◽  
Yohann Duverger ◽  
Allison Huguenot ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Proton Motive Force ◽  
Iron Limitation ◽  
Ros Production ◽  
Oxygen Species ◽  
Fenton Chemistry ◽  
Respiratory Complexes ◽  
Iron Sulfur ◽  
Cluster Biosynthesis

All bactericidal antibiotics were recently proposed to kill by inducing reactive oxygen species (ROS) production, causing destabilization of iron-sulfur (Fe-S) clusters and generating Fenton chemistry. We find that the ROS response is dispensable upon treatment with bactericidal antibiotics. Furthermore, we demonstrate that Fe-S clusters are required for killing only by aminoglycosides. In contrast to cells, using the major Fe-S cluster biosynthesis machinery, ISC, cells using the alternative machinery, SUF, cannot efficiently mature respiratory complexes I and II, resulting in impendence of the proton motive force (PMF), which is required for bactericidal aminoglycoside uptake. Similarly, during iron limitation, cells become intrinsically resistant to aminoglycosides by switching from ISC to SUF and down-regulating both respiratory complexes. We conclude that Fe-S proteins promote aminoglycoside killing by enabling their uptake.

scholarly journals Reactive oxygen species are required for spore-wall formation in Physcomitrella patens

Botany ◽  
2020 ◽  
Vol 98 (10) ◽  
pp. 575-587
Author(s):  
Fazle Rabbi ◽  
Karen S. Renzaglia ◽  
Neil W. Ashton ◽  
Dae-Yeon Suh
Keyword(s):  
Reactive Oxygen Species ◽  
Physcomitrella Patens ◽  
Reactive Oxygen ◽  
Spore Wall ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Normal Wall ◽  
Spore Walls ◽  
Ros Scavenger ◽  
Spine Structure

A robust spore wall was a key requirement for terrestrialization by early plants. Sporopollenin in spore and pollen grain walls is thought to be polymerized and cross-linked to other macromolecular components, partly through oxidative processes involving H2O2. Therefore, we investigated effects of scavengers of reactive oxygen species (ROS) on the formation of spore walls in the moss Physcomitrella patens (Hedw.) Bruch, Schimp & W. Gümbel. Exposure of sporophytes, containing spores in the process of forming walls, to ascorbate, dimethylthiourea, or 4-hydroxy-TEMPO prevented normal wall development in a dose, chemical, and stage-dependent manner. Mature spores, exposed while developing to a ROS scavenger, burst when mounted in water on a flat slide under a coverslip (a phenomenon we named “augmented osmolysis” because they did not burst in phosphate-buffered saline or in water on a depression slide). Additionally, the walls of exposed spores were more susceptible to alkaline hydrolysis than those of the control spores, and some were characterized by discontinuities in the exine, anomalies in perine spine structure, abnormal intine and aperture, and occasionally, wall shedding. Our data support the involvement of oxidative cross-linking in spore-wall development, including sporopollenin polymerization or deposition, as well as a role for ROS in intine/aperture development.

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