The Protective Role of 1,8-Dihydroxynaphthalene–Melanin on Conidia of the Opportunistic Human Pathogen Aspergillus fumigatus Revisited: No Role in Protection against Hydrogen Peroxide and Superoxides

Opportunistic pathogens like Aspergillus fumigatus have strategies to protect themselves against reactive oxygen species like hydrogen peroxides and superoxides that are produced by immune cells. DHN-melanin is the green pigment on conidia of Aspergillus fumigatus and more than 2 decades ago was reported to protect conidia against hydrogen peroxide.

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Cyclo-(L-Phe-L-Pro), a Quorum-Sensing Signal ofVibrio vulnificus, Induces Expression of Hydroperoxidase through a ToxR-LeuO-HU-RpoS Signaling Pathway To Confer Resistance against Oxidative Stress

Infection and Immunity ◽

10.1128/iai.00932-17 ◽

2018 ◽

Vol 86 (9) ◽

Cited By ~ 3

Author(s):

In Hwang Kim ◽

So-Yeon Kim ◽

Na-Young Park ◽

Yancheng Wen ◽

Keun-Woo Lee ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Virulence Factor ◽

Vibrio Vulnificus ◽

Transcriptional Regulator ◽

Oxygen Species ◽

Human Pathogen ◽

Content Type ◽

Opportunistic Human Pathogen ◽

Bacterial Genes

ABSTRACTVibrio vulnificus, an opportunistic human pathogen, produces cyclo-(l-Phe-l-Pro) (cFP), which serves as a signaling molecule controlling the ToxR-dependent expression of innate bacterial genes, and also as a virulence factor eliciting pathogenic effects on human cells by enhancing intracellular reactive oxygen species levels. We found that cFP facilitated the protection ofV. vulnificusagainst hydrogen peroxide. At a concentration of 1 mM, cFP enhanced the level of the transcriptional regulator RpoS, which in turn induced expression ofkatG, encoding hydroperoxidase I, an enzyme that detoxifies H2O2to overcome oxidative stress. We found that cFP upregulated the transcription of the histone-like proteins vHUα and vHUβ through the cFP-dependent regulator LeuO. LeuO binds directly to upstream regions ofvhuAandvhuBto enhance transcription. vHUα and vHUβ then enhance the level of RpoS posttranscriptionally by stabilizing the mRNA. This cFP-mediated ToxR-LeuO-vHUαβ-RpoS pathway also upregulates genes known to be members of the RpoS regulon, suggesting that cFP acts as a cue for the signaling pathway responsible for both the RpoS and the LeuO regulons. Taken together, this study shows that cFP plays an important role as a virulence factor, as well as a signal for the protection of the cognate pathogen.

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Role of Common γ-Chain Cytokines in Lung Interleukin-22 Regulation after Acute Exposure to Aspergillus fumigatus

Infection and Immunity ◽

10.1128/iai.00157-18 ◽

2018 ◽

Vol 86 (10) ◽

Cited By ~ 3

Author(s):

Kristen M. Reeder ◽

Joseph J. Mackel ◽

Matthew S. Godwin ◽

Chad W. Dunaway ◽

Jonathan P. Blackburn ◽

...

Keyword(s):

T Cells ◽

Aspergillus Fumigatus ◽

Γδ T Cells ◽

Protective Role ◽

Lymphoid Cells ◽

Inkt Cells ◽

Content Type ◽

Interleukin 22 ◽

Cell Sources

ABSTRACT Humans are constantly exposed to the opportunistic mold Aspergillus fumigatus, and disease caused by this pathogen is often determined by the magnitude of local and systemic immune responses. We have previously shown a protective role for interleukin-22 (IL-22) after acute A. fumigatus exposure. Here, employing IL-22Cre R26ReYFP reporter mice, we identified iNKT cells, γδ T cells, and type 3 innate lymphoid cells (ILC3s) as lung cell sources of IL-22 in response to acute A. fumigatus exposure. As these cells often utilize common γ-chain cytokines for their development or maintenance, we determined the role of IL-7, IL-21, and IL-15 in lung IL-22 induction and A. fumigatus lung clearance. We observed that IL-7, IL-21, and IL-15 were essential for, partially required for, or negatively regulated the production of IL-22, respectively. Deficiency in IL-7 and IL-21, but not IL-15R, resulted in impaired fungal clearance. Surprisingly, however, the absence of IL-7, IL-21, or IL-15R signaling had no effect on neutrophil recruitment. The levels of IL-1α, an essential anti-A. fumigatus proinflammatory cytokine, were increased in the absence of IL-7 and IL-15R but decreased in the absence of IL-21. IL-7 was responsible for maintaining lung iNKT cells and γδ T cells, whereas IL-21 was responsible for maintaining lung iNKT cells and ILC3s. In contrast, IL-15R deficiency had no effect on the absolute numbers of any IL-22 cell source, rather resulting in enhanced per cell production of IL-22 by iNKT cells and γδ T cells. Collectively, these results provide insight into how the IL-22 response in the lung is shaped after acute A. fumigatus exposure.

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Genome Sequences of Two Strains of the Food Spoilage Mold Aspergillus fischeri

Microbiology Resource Announcements ◽

10.1128/mra.01328-19 ◽

2019 ◽

Vol 8 (50) ◽

Cited By ~ 1

Author(s):

Shu Zhao ◽

Jean-Paul Latgé ◽

John G. Gibbons

Keyword(s):

Comparative Genomics ◽

Aspergillus Fumigatus ◽

Close Relative ◽

Food Spoilage ◽

Human Pathogen ◽

Genome Sequences ◽

Content Type ◽

Aspergillus Fischeri ◽

Common Food ◽

Opportunistic Human Pathogen

Aspergillus fischeri is a common food spoilage fungus and a close relative of the opportunistic human pathogen Aspergillus fumigatus. Here, we sequenced the genomes of two isolates of A. fischeri to build resources for comparative genomics and to aid in differentiation between A. fischeri subspecies.

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Contributions of Spore Secondary Metabolites to UV-C Protection and Virulence Vary in Different Aspergillus fumigatus Strains

mBio ◽

10.1128/mbio.03415-19 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Adriana Blachowicz ◽

Nicholas Raffa ◽

Jin Woo Bok ◽

Tsokyi Choera ◽

Benjamin Knox ◽

...

Keyword(s):

Secondary Metabolites ◽

Invasive Aspergillosis ◽

Aspergillus Fumigatus ◽

Uv Radiation ◽

Human Pathogen ◽

Zebrafish Model ◽

Protective Properties ◽

Content Type ◽

Uv C

ABSTRACT Fungi are versatile organisms which thrive in hostile environments, including the International Space Station (ISS). Several isolates of the human pathogen Aspergillus fumigatus have been found contaminating the ISS, an environment with increased exposure to UV radiation. Secondary metabolites (SMs) in spores, such as melanins, have been shown to protect spores from UV radiation in other fungi. To test the hypothesis that melanin and other known spore SMs provide UV protection to A. fumigatus isolates, we subjected SM spore mutants to UV-C radiation. We found that 1,8-dihydroxynaphthalene (DHN)-melanin mutants of two clinical A. fumigatus strains (Af293 and CEA17) but not an ISS-isolated strain (IF1SW-F4) were more sensitive to UV-C than their respective wild-type (WT) strains. Because DHN-melanin has been shown to shield A. fumigatus from the host immune system, we examined all DHN mutants for virulence in the zebrafish model of invasive aspergillosis. Following recent studies highlighting the pathogenic variability of different A. fumigatus isolates, we found DHN-melanin to be a virulence factor in CEA17 and IF1SW-F4 but not Af293. Three additional spore metabolites were examined in Af293, where fumiquinazoline also showed UV-C-protective properties, but two other spore metabolites, monomethylsulochrin and fumigaclavine, provided no UV-C-protective properties. Virulence tests of these three SM spore mutants indicated a slight increase in virulence of the monomethylsulochrin deletion strain. Taken together, this work suggests differential roles of specific spore metabolites across Aspergillus isolates and by types of environmental stress. IMPORTANCE Fungal spores contain secondary metabolites that can protect them from a multitude of abiotic and biotic stresses. Conidia (asexual spores) of the human pathogen Aspergillus fumigatus synthesize several metabolites, including melanin, which has been reported to be important for virulence in this species and to be protective against UV radiation in other fungi. Here, we investigate the role of melanin in diverse isolates of A. fumigatus and find variability in its ability to protect spores from UV-C radiation or impact virulence in a zebrafish model of invasive aspergillosis in two clinical strains and one ISS strain. Further, we assess the role of other spore metabolites in a clinical strain of A. fumigatus and identify fumiquinazoline as an additional UV-C-protective molecule but not a virulence determinant. The results show differential roles of secondary metabolites in spore protection dependent on the environmental stress and strain of A. fumigatus. As protection from elevated levels of radiation is of paramount importance for future human outer space explorations, the discovery of small molecules with radiation-protective potential may result in developing novel safety measures for astronauts.

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Role of Bacillus subtilis DNA Glycosylase MutM in Counteracting Oxidatively Induced DNA Damage and in Stationary-Phase-Associated Mutagenesis

Journal of Bacteriology ◽

10.1128/jb.00147-15 ◽

2015 ◽

Vol 197 (11) ◽

pp. 1963-1971 ◽

Cited By ~ 13

Author(s):

Martha Gómez-Marroquín ◽

Luz E. Vidales ◽

Bernardo N. Debora ◽

Fernando Santos-Escobar ◽

Armando Obregón-Herrera ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Hydrogen Peroxide ◽

Dna Damage ◽

Bacillus Subtilis ◽

Stationary Phase ◽

Reactive Oxygen ◽

Dna Glycosylase ◽

Oxygen Species ◽

Content Type

ABSTRACTReactive oxygen species (ROS) promote the synthesis of the DNA lesion 8-oxo-G, whose mutagenic effects are counteracted in distinct organisms by the DNA glycosylase MutM. We report here that inBacillus subtilis,mutMis expressed during the exponential and stationary phases of growth. In agreement with this expression pattern, results of a Western blot analysis confirmed the presence of MutM in both stages of growth. In comparison with cells of a wild-type strain, cells ofB. subtilislacking MutM increased their spontaneous mutation frequency to Rifrand were more sensitive to the ROS promoter agents hydrogen peroxide and 1,1′-dimethyl-4,4′-bipyridinium dichloride (Paraquat). However, despite MutM's proven participation in preventing ROS-induced-DNA damage, the expression ofmutMwas not induced by hydrogen peroxide, mitomycin C, or NaCl, suggesting that transcription of this gene is not under the control of the RecA, PerR, or σBregulons. Finally, the role of MutM in stationary-phase-associated mutagenesis (SPM) was investigated in the strainB. subtilisYB955 (hisC952 metB5 leuC427). Results revealed that under limiting growth conditions, amutMknockout strain significantly increased the amount of stationary-phase-associatedhis,met, andleurevertants produced. In summary, our results support the notion that the absence of MutM promotes mutagenesis that allows nutritionally stressedB. subtiliscells to escape from growth-limiting conditions.IMPORTANCEThe present study describes the role played by a DNA repair protein (MutM) in protecting the soil bacteriumBacillus subtilisfrom the genotoxic effects induced by reactive oxygen species (ROS) promoter agents. Moreover, it reveals that the genetic inactivation ofmutMallows nutritionally stressed bacteria to escape from growth-limiting conditions, putatively by a mechanism that involves the accumulation and error-prone processing of oxidized DNA bases.

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ROS Defense Systems and Terminal Oxidases in Bacteria

Antioxidants ◽

10.3390/antiox10060839 ◽

2021 ◽

Vol 10 (6) ◽

pp. 839

Author(s):

Vitaliy B. Borisov ◽

Sergey A. Siletsky ◽

Martina R. Nastasi ◽

Elena Forte

Keyword(s):

Defense Mechanisms ◽

Protective Role ◽

Superoxide Dismutases ◽

Oxygen Species ◽

Ros Scavenging ◽

Terminal Oxidases ◽

Defense Systems ◽

Respiratory Chains ◽

Scavenging Enzymes

Reactive oxygen species (ROS) comprise the superoxide anion (O2·−), hydrogen peroxide (H2O2), hydroxyl radical (·OH), and singlet oxygen (1O2). ROS can damage a variety of macromolecules, including DNA, RNA, proteins, and lipids, and compromise cell viability. To prevent or reduce ROS-induced oxidative stress, bacteria utilize different ROS defense mechanisms, of which ROS scavenging enzymes, such as superoxide dismutases, catalases, and peroxidases, are the best characterized. Recently, evidence has been accumulating that some of the terminal oxidases in bacterial respiratory chains may also play a protective role against ROS. The present review covers this role of terminal oxidases in light of recent findings.

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Complete Genome Sequence of Stenotrophomonas Phage Mendera

Microbiology Resource Announcements ◽

10.1128/mra.01411-19 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Kameron D. Garza ◽

Heather Newkirk ◽

Russell Moreland ◽

Carlos F. Gonzalez ◽

Mei Liu ◽

...

Keyword(s):

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Stenotrophomonas Maltophilia ◽

Human Pathogen ◽

Base Pairs ◽

Content Type ◽

Genomic Annotation ◽

Opportunistic Human Pathogen

Stenotrophomonas maltophilia is an emerging opportunistic human pathogen. In this report, we describe the isolation and genomic annotation of the S. maltophilia-infecting bacteriophage Mendera. A myophage of 159,961 base pairs, Mendera is T4-like and related most closely to Stenotrophomonas phage IME-SM1.

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Oxidative Stress Correlates with Wolbachia-Mediated Antiviral Protection in Wolbachia-Drosophila Associations

Applied and Environmental Microbiology ◽

10.1128/aem.03847-14 ◽

2015 ◽

Vol 81 (9) ◽

pp. 3001-3005 ◽

Cited By ~ 42

Author(s):

Zhee Sheen Wong ◽

Jeremy C. Brownlie ◽

Karyn N. Johnson

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Biocontrol Agent ◽

Oxygen Species ◽

Content Type ◽

Host Insect ◽

Fitness Traits ◽

Endogenous Reactive Oxygen Species ◽

Potential Biocontrol Agent ◽

Definition Of

ABSTRACTWolbachiamediates antiviral protection in insect hosts and is being developed as a potential biocontrol agent to reduce the spread of insect-vectored viruses. Definition of the molecular mechanism that generates protection is important for understanding the tripartite interaction between host insect,Wolbachia, and virus. Elevated oxidative stress was previously reported for a mosquito line experimentally infected withWolbachia, suggesting that oxidative stress is important forWolbachia-mediated antiviral protection. However,Wolbachiaexperimentally introduced into mosquitoes impacts a range of host fitness traits, some of which are unrelated to antiviral protection. To explore whether elevated oxidative stress is associated with antiviral protection inWolbachia-infected insects, we analyzed oxidative stress of fiveWolbachia-infectedDrosophilalines. In flies infected with protectiveWolbachiastrains, hydrogen peroxide concentrations were 1.25- to 2-fold higher than those in paired fly lines cured ofWolbachiainfection. In contrast, there was no difference in the hydrogen peroxide concentrations in flies infected with nonprotectiveWolbachiastrains compared to flies cured ofWolbachiainfection. Using aDrosophilamutant that produces increased levels of hydrogen peroxide, we investigated whether flies with high levels of endogenous reactive oxygen species had altered responses to virus infection and found that flies with high levels of endogenous hydrogen peroxide were less susceptible to virus-induced mortality. Taken together, these results suggest that elevated oxidative stress correlates withWolbachia-mediated antiviral protection in naturalDrosophilahosts.

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Bacteriophages LIMElight and LIMEzero of Pantoea agglomerans, Belonging to the “phiKMV-Like Viruses”

Applied and Environmental Microbiology ◽

10.1128/aem.00128-11 ◽

2011 ◽

Vol 77 (10) ◽

pp. 3443-3450 ◽

Cited By ~ 35

Author(s):

Evelien M. Adriaenssens ◽

Pieter-Jan Ceyssens ◽

Vincent Dunon ◽

Hans-Wolfgang Ackermann ◽

Johan Van Vaerenbergh ◽

...

Keyword(s):

Soil Samples ◽

Pantoea Agglomerans ◽

Open Reading Frames ◽

Human Pathogen ◽

Content Type ◽

Host Diversity ◽

Double Stranded Dna ◽

Opportunistic Human Pathogen ◽

Reading Frames

ABSTRACTPantoea agglomeransis a common soil bacterium used in the biocontrol of fungi and bacteria but is also an opportunistic human pathogen. It has been described extensively in this context, but knowledge of bacteriophages infecting this species is limited. Bacteriophages LIMEzero and LIMElight ofP. agglomeransare lytic phages, isolated from soil samples, belonging to thePodoviridaeand are the firstPantoeaphages of this family to be described. The double-stranded DNA (dsDNA) genomes (43,032 bp and 44,546 bp, respectively) encode 57 and 55 open reading frames (ORFs). Based on the presence of an RNA polymerase in their genomes and their overall genome architecture, these phages should be classified in the subfamily of theAutographivirinae, within the genus of the “phiKMV-like viruses.” Phylogenetic analysis of all the sequenced members of theAutographivirinaesupports the classification of phages LIMElight and LIMEzero as members of the “phiKMV-like viruses” and corroborates the subdivision into the different genera. These data expand the knowledge ofPantoeaphages and illustrate the wide host diversity of phages within the “phiKMV-like viruses.”

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