scholarly journals 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

2018 ◽  
Vol 86 (9) ◽  
Author(s):  
In Hwang Kim ◽  
So-Yeon Kim ◽  
Na-Young Park ◽  
Yancheng Wen ◽  
Keun-Woo Lee ◽  
...  

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.

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.


2018 ◽  
Vol 200 (16) ◽  
Author(s):  
Daniel M. Chodur ◽  
Dean A. Rowe-Magnus

ABSTRACT Vibrio vulnificus is a potent opportunistic human pathogen that contaminates the human food chain by asymptomatically colonizing seafood. The expression of the 9-gene brp exopolysaccharide locus mediates surface adherence and is controlled by the secondary signaling molecule c-di-GMP and the regulator BrpT. Here, we show that c-di-GMP and BrpT also regulate the expression of an adjacent 5-gene cluster that includes the cabABC operon, brpT, and another VpsT-like transcriptional regulator gene, brpS. The expression of the 14 genes spanning the region increased with elevated intracellular c-di-GMP levels in a BrpT-dependent manner, save for brpS, which was positively regulated by c-di-GMP and repressed by BrpT. BrpS repressed brpA expression and was required for rugose colony development. The mutation of its consensus WFSA c-di-GMP binding motif blocked these activities, suggesting that BrpS function is dependent on binding c-di-GMP. BrpT specifically bound the cabA, brpT, and brpS promoters, and binding sites homologous to the Vibrio cholerae VpsT binding site were identified upstream of brpA and brpT. Transcription was initiated distal to brpA, and a conserved RfaH-recruiting ops element and a potential Rho utilization (rut) terminator site were identified within the 100-bp leader region, suggesting the integration of early termination and operon polarity suppression into the regulation of brp transcription. The GC content and codon usage of the 16-kb brp region was 5.5% lower relative to that of the flanking DNA, suggesting its recent assimilation via horizontal transfer. Thus, architecturally, the brp region can be considered an acquired biofilm and rugosity island that is subject to complex regulation. IMPORTANCE Biofilm and rugose colony formation are developmental programs that underpin the evolution of Vibrio vulnificus as a potent opportunistic human pathogen and successful environmental organism. A better understanding of the regulatory pathways governing theses phenotypes promotes the development and implementation of strategies to mitigate food chain contamination by this pathogen. c-di-GMP signaling is central to both pathways. We show that the molecule orchestrates the expression of 14 genes clustered in a 16-kb segment of the genome that governs biofilm and rugose colony development. This region exhibits the hallmarks of horizontal transfer, suggesting complex regulatory control of a recently assimilated genetic island governing the colonization response of V. vulnificus.


mSphere ◽  
2022 ◽  
Author(s):  
E. M. Keizer ◽  
I. D. Valdes ◽  
B. L. McCann ◽  
E. M. Bignell ◽  
H. A. B. Wösten ◽  
...  

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.


2019 ◽  
Vol 7 (12) ◽  
pp. 631 ◽  
Author(s):  
Kazuya Morikawa ◽  
Yuri Ushijima ◽  
Ryosuke L. Ohniwa ◽  
Masatoshi Miyakoshi ◽  
Kunio Takeyasu

The evolutionary success of Staphylococcus aureus as an opportunistic human pathogen is largely attributed to its prominent abilities to cope with a variety of stresses and host bactericidal factors. Reactive oxygen species are important weapons in the host arsenal that inactivate phagocytosed pathogens, but S. aureus can survive in phagosomes and escape from phagocytic cells to establish infections. Molecular genetic analyses combined with atomic force microscopy have revealed that the MrgA protein (part of the Dps family of proteins) is induced specifically in response to oxidative stress and converts the nucleoid from the fibrous to the clogged state. This review collates a series of evidences on the staphylococcal nucleoid dynamics under oxidative stress, which is functionally and physically distinct from compacted Escherichia coli nucleoid under stationary phase. In addition, potential new roles of nucleoid clogging in the staphylococcal life cycle will be proposed.


2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Hui Wang ◽  
Nawar Naseer ◽  
Yaran Chen ◽  
Anthony Y. Zhu ◽  
Xuewen Kuai ◽  
...  

ABSTRACT Bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. The human pathogen Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, utilizes the transcriptional regulator OxyR to activate genes related to oxidative stress resistance, including peroxiredoxin PrxA, in response to hydrogen peroxide. In this study, we identified another OxyR homolog in V. cholerae, which we named OxyR2, and we renamed the previous OxyR OxyR1. We found that OxyR2 is required to activate its divergently transcribed gene ahpC, encoding an alkylhydroperoxide reductase, independently of H2O2. A conserved cysteine residue in OxyR2 is critical for this function. Mutation of either oxyR2 or ahpC rendered V. cholerae more resistant to H2O2. RNA sequencing analyses indicated that OxyR1-activated oxidative stress-resistant genes were highly expressed in oxyR2 mutants even in the absence of H2O2. Further genetic analyses suggest that OxyR2-activated AhpC modulates OxyR1 activity by maintaining low intracellular concentrations of H2O2. Furthermore, we showed that ΔoxyR2 and ΔahpC mutants were less fit when anaerobically grown bacteria were exposed to low levels of H2O2 or incubated in seawater. These results suggest that OxyR2 and AhpC play important roles in the V. cholerae oxidative stress response.


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.


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Kameron D. Garza ◽  
Heather Newkirk ◽  
Russell Moreland ◽  
Carlos F. Gonzalez ◽  
Mei Liu ◽  
...  

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.


2015 ◽  
Vol 81 (9) ◽  
pp. 3001-3005 ◽  
Author(s):  
Zhee Sheen Wong ◽  
Jeremy C. Brownlie ◽  
Karyn N. Johnson

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.


2011 ◽  
Vol 77 (10) ◽  
pp. 3443-3450 ◽  
Author(s):  
Evelien M. Adriaenssens ◽  
Pieter-Jan Ceyssens ◽  
Vincent Dunon ◽  
Hans-Wolfgang Ackermann ◽  
Johan Van Vaerenbergh ◽  
...  

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.”


2021 ◽  
Vol 7 (7) ◽  
Author(s):  
Prashant P. Patil ◽  
Sanjeet Kumar ◽  
Amandeep Kaur ◽  
Samriti Midha ◽  
Kanika Bansal ◽  
...  

Stenotrophomonas maltophilia is a typical example of an environmental originated opportunistic human pathogen, which can thrive at different habitats including the human body and can cause a wide range of infections. It must cope with heat stress during transition from the environment to the human body as the physiological temperature of the human body (37 °C) is higher than environmental niches (22–30 °C). Interestingly, S. rhizophila a phylogenetic neighbour of S. maltophilia within genus Stenotrophomonas is unable to grow at 37 °C. Thus, it is crucial to understand how S. maltophilia is adapted to human body temperature, which could suggest its evolution as an opportunistic human pathogen. In this study, we have performed comparative transcriptome analysis of S. maltophilia grown at 28 and 37 °C as temperature representative for environmental niches and the human body, respectively. RNA-Seq analysis revealed several interesting findings showing alterations in gene-expression levels at 28 and 37 °C, which can play an important role during infection. We have observed downregulation of genes involved in cellular motility, energy production and metabolism, replication and repair whereas upregulation of VirB/D4 type IV secretion system, aerotaxis, cation diffusion facilitator family transporter and LacI family transcriptional regulators at 37 °C. Microscopy and plate assays corroborated altered expression of genes involved in motility. The results obtained enhance our understanding of the strategies employed by S. maltophilia during adaptation towards the human body.


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