Regulation of haemolysin (<scp>VvhA</scp>) production by ferric uptake regulator (<scp>Fur</scp>) in <i><scp>V</scp>ibrio vulnificus</i>: repression of <i>vvhA</i> transcription by <scp>Fur</scp> and proteolysis of <scp>VvhA</scp> by <scp>Fur</scp>‐repressive exoproteases

Lee, Hyunjung; Kim, Jeong‐A; Lee, Mi-Ae; Park, Soon‐Jung; Lee, Kyu‐Ho

doi:10.1111/mmi.12224

Cited by 32 publications

(37 citation statements)

References 54 publications

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“…VvpS was shown to be an autolytic exoprotease, of which C-terminal domain has a hydrolyzing activity toward peptidoglycan. Recently, an exoprotease VvpM, which is presumed to be a zinc-metalloprotease, has been isolated from the culture supernatants of V. vulnificus (Lee et al, 2013). The present study shows that this newly identified VvpM caused death of the human cells accompanying changes in cellular morphologies indicating an apoptosis.…”

Section: Introductionmentioning

confidence: 50%

VvpM, an extracellular metalloprotease of Vibrio vulnificus, induces apoptotic death of human cells

et al. 2014

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A pathogenic bacterium, Vibrio vulnificus produces various extracellular proteases including the elastolytic metalloprotease, VvpE. In silico analysis of its genome revealed a VvpE-homologous protease, VvpM whose proteolytic activity was abolished by specific inhibitors against metalloproteases. To investigate whether this newly identified protease has pathogenic role in host interaction in addition to proteolytic role, human cell lines were incubated with recombinant VvpM (rVvpM). rVvpM-challenged cells showed typical morphological changes found in cells under apoptosis. Apoptotic cell death was further evidenced by estimating the Annexin V-stained cells, whose proportions were dependent upon the concentrations of rVvpM treated to human cells. To elucidate the signaling pathway for VvpM-induced apoptosis, three MAPKs were tested if their activation were mediated by rVvpM. ERK1/2 was phosphorylated by treatment of rVvpM and rVvpM-induced cell death was blocked by a specific inhibitor against ERK1/2. In rVvpM-treated cells, the cytosolic levels of cytochrome c were increased in a VvpM concentration-dependent manner, while the levels of cytochrome c in mitochondria were decreased. Cell deaths were accompanied by apparent cleavages of procaspases-9 and -3 to the active caspases-9 and -3, respectively. Therefore, this study demonstrates that an extracellular metalloprotease of V. vulnificus, VvpM induces apoptosis of human cells via a pathway consisting of ERK activation, cytochrome c release, and then activation of caspases-9 and -3.

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Section: Introductionmentioning

confidence: 50%

VvpM, an extracellular metalloprotease of Vibrio vulnificus, induces apoptotic death of human cells

et al. 2014

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“…For a hemolysis assay, an aliquot of the culture supernatants of V. vulnificus strains grown to an A 600 of 0.9 was mixed with an equal volume of human red blood cell (hRBC) suspension (1.0% in phosphate-buffered saline) (Innovative Research, Novi, MI) and incubated at 37°C for 20 min. The level of hemolysis was determined as described elsewhere (30) and expressed using the complete hemolysis by 1% Triton X-100 as 100%.…”

Section: Quantitative Real-time Pcr (Qrt-pcr)mentioning

confidence: 99%

IscR Is a Global Regulator Essential for Pathogenesis of Vibrio vulnificus and Induced by Host Cells

Lim

Choi

2014

Infect Immun

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A mutant that exhibited less cytotoxic activity toward INT-407 human intestinal epithelial cells than the wild type was screened from a random transposon mutant library of Vibrio vulnificus, and an open reading frame encoding an Fe-S cluster regulator, IscR, was identified using a transposon-tagging method. A mutational analysis demonstrated that IscR contributes to mouse mortality as well as cytotoxicity toward the INT-407 cells, indicating that IscR is essential for the pathogenesis of V. vulnificus. A whole-genome microarray analysis revealed that IscR influenced the expression of 67 genes, of which 52 were upregulated and 15 were downregulated. Among these, 12 genes most likely involved in motility and adhesion to host cells, hemolytic activity, and survival under oxidative stress of the pathogen during infection were selected and experimentally verified to be upregulated by IscR. Accordingly, the disruption of iscR resulted in a significant reduction in motility and adhesion to INT-407 cells, in hemolytic activity, and in resistance to reactive oxygen species (ROS) such as H 2 O 2 and tert-butyl hydroperoxide (t-BOOH). Furthermore, the present study demonstrated that iscR expression was induced by exposure of V. vulnificus to the INT-407 cells, and the induction appeared to be mediated by ROS generated by the host cells during infection. Consequently, the combined results indicated that IscR is a global regulator that contributes to the overall success in the pathogenesis of V. vulnificus by regulating the expression of various virulence and survival genes in addition to Fe-S cluster genes. Most of virulence factors of pathogenic bacteria act cooperatively to obtain maximum effectiveness during pathogenesis while their expression is coordinately regulated by common global regulators in response to environmental conditions, and this coordinated regulation facilitates the cooperation of virulence factors and is crucial to the overall success of the pathogens during infection (1, 2). Vibrio vulnificus is an opportunistic Gram-negative pathogen that frequently contaminates oysters. It has been proposed that numerous virulence factors account for the fulminating and destructive nature of V. vulnificus infections and contribute to not only disease development but also the survival and multiplication on or within the host (for a recent review, see reference 3). However, studies about global regulators involved in the regulation of V. vulnificus virulence factors are still very limited.Iron-sulfur proteins containing the Fe-S cluster as a cofactor carry out multiple important cellular processes such as electron transfer, metabolic reactions, and gene regulation and are widely distributed (for recent reviews, see references 4 and 5). A highly conserved isc operon, iscRSUA-hscBA-fdx, was discovered to encode all of the proteins required for the biogenesis of the majority, if not all, of the Fe-S cluster proteins in Escherichia coli (for recent reviews, see references 5 and 6). Expression of the isc operon is autoregu...

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“…Fur has been shown to play similar roles in V. vulnificus (214)(215)(216), V. anguillarum (217,218), and V. salmonicida (219). In each of these vibrios, Fur negatively regulates the expression of genes for iron acquisition systems, thereby reducing the chance of toxicity due to iron overload.…”

Section: Regulation Of Iron Transport Systemsmentioning

confidence: 99%

“…Fur negatively regulates the expression of hemolysins in V. cholerae (220), V. parahaemolyticus (221), and V. vulnificus (215). V. vulnificus produces a protease that aids in the acquisition of heme from heme-albumin (222).…”

Section: Regulation Of Iron Transport Systemsmentioning

confidence: 99%

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

Payne

Mey

Wyckoff

2016

Microbiol Mol Biol Rev

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SUMMARYIron is an essential element forVibriospp., but the acquisition of iron is complicated by its tendency to form insoluble ferric complexes in nature and its association with high-affinity iron-binding proteins in the host. Vibrios occupy a variety of different niches, and each of these niches presents particular challenges for acquiring sufficient iron.Vibriospecies have evolved a wide array of iron transport systems that allow the bacteria to compete for this essential element in each of its habitats. These systems include the secretion and uptake of high-affinity iron-binding compounds (siderophores) as well as transport systems for iron bound to host complexes. Transporters for ferric and ferrous iron not complexed to siderophores are also common toVibriospecies. Some of the genes encoding these systems show evidence of horizontal transmission, and the ability to acquire and incorporate additional iron transport systems may have allowedVibriospecies to more rapidly adapt to new environmental niches. While too little iron prevents growth of the bacteria, too much can be lethal. The appropriate balance is maintained in vibrios through complex regulatory networks involving transcriptional repressors and activators and small RNAs (sRNAs) that act posttranscriptionally. Examination of the number and variety of iron transport systems found inVibriospp. offers insights into how this group of bacteria has adapted to such a wide range of habitats.

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Regulation of haemolysin (VvhA) production by ferric uptake regulator (Fur) in Vibrio vulnificus: repression of vvhA transcription by Fur and proteolysis of VvhA by Fur‐repressive exoproteases

Cited by 32 publications

References 54 publications

VvpM, an extracellular metalloprotease of Vibrio vulnificus, induces apoptotic death of human cells

VvpM, an extracellular metalloprotease of Vibrio vulnificus, induces apoptotic death of human cells

IscR Is a Global Regulator Essential for Pathogenesis of Vibrio vulnificus and Induced by Host Cells

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

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