Involvement of Vulnibactin and Exocellular Protease in Utilization of Transferrin‐ and Lactoferrin‐Bound Iron by <i>Vibrio vulnificus</i>

Okujo, Noriyuki; Akiyama, Toshihito; Miyoshi, Shin Ichi; Shinoda, Sumió; Yamamoto, Satoshi

doi:10.1111/j.1348-0421.1996.tb01114.x

Cited by 52 publications

(58 citation statements)

References 28 publications

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“…Although it is essential for iron-assimilation, vulnibactin can remove iron only from transferrin digested by VVP [32]. The present study, in which VVP production was observed even at early growth phase, may support our previous conclusion.…”

supporting

confidence: 82%

High growing ability of Vibrio vulnificus biotype 1 is essential for production of a toxic metalloprotease causing systemic diseases in humans

Watanabe

Miyoshi

Kawase

et al. 2004

Microbial Pathogenesis

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Vibrio vulnificus biotype 1, a causative agent of fatal septicemia or wound infection in humans, is known to produce a toxic metalloprotease as an important virulence determinant. V. vulnificus biotype 2 (serovar E), a primary eel pathogen, was found to elaborate an extracellular metalloprotease that was indistinguishable from that of biotype 1. The potential of V. vulnificus biotype 1 for production of the metalloprotease was compared with biotype 2 and other human non-pathogenic Vibrio species (V. anguillarum and V. proteolyticus). When cultivated at 25o C in tryptone-yeast extract broth supplemented with 0.9 % NaCl, all bacteria multiplied sufficiently and secreted significant amounts of the metalloprotease. However, at 37 o C with 0.9 % NaCl, V.anguillarum neither grew nor produced the metalloprotease. In human serum, only V.vulnificus biotype 1 revealed a steady multiplication accompanied with production of the extracellular metalloprotease. This prominent ability of biotype 1 in growth and protease production may contribute to cause serious systemic diseases in humans.

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supporting

confidence: 82%

High growing ability of Vibrio vulnificus biotype 1 is essential for production of a toxic metalloprotease causing systemic diseases in humans

Watanabe

Miyoshi

Kawase

et al. 2004

Microbial Pathogenesis

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“…15,16) However, in this study, purified VvpE was exogenously added to a culture medium in order to induce the proteolytic cleavage of transferrin or lactoferrin at culture initiation, which does not accurately simulate VvpE production during batch culture. In our previous study, 20) we argued that VvpE plays a role in iron-uptake from HT.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] Of the various biological activities of VvpE, its role in facilitating V. vulnificus iron-uptake via the proteolytic cleavage of heme proteins, transferrins, and lactoferrins has attracted some attention. 15,16) However, our previous study demonstrated that an insertional mutation of vvpE gene has no direct effect on iron-assimilation from human transferrins. 20) Bacterial iron-uptake systems are themselves virulence factors in many bacterial pathogens, and are promising vaccine targets.…”

mentioning

confidence: 99%

“…[1][2][3]15,16) However, the role of VvpE in the pathogenesis of VVS remains unclear, as VvpE-deficient mutants showed comparable or higher virulence than wild type strains in mouse experimental models. [17][18][19] Of the various biological activities of VvpE, its role in facilitating V. vulnificus iron-uptake via the proteolytic cleavage of heme proteins, transferrins, and lactoferrins has attracted some attention.…”

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confidence: 99%

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Vibrio vulnificus Vulnibactin, But Not Metalloprotease VvpE, Is Essentially Required for Iron-Uptake from Human Holotransferrin

Kim

Park

et al. 2006

Biological & Pharmaceutical Bulletin

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Vibrio vulnificus is a gram-negative halophilic estuarine bacterium. The pathogen causes fatal and rapidly-progressing septicemia with high mortality. This V. vulnificus septicemia (VVS) is closely associated with the consumption of raw seafood contaminated with the bacterium in patients with underlying hepatic disease, heavy alcohol-drinking habits, or other immunocompromised conditions. Several putative virulence factors including capsule, hemolysin, protease, and iron-assimilation systems have been suggested to be associated with VVS, but only capsule and iron-assimilation systems have been confirmed to be authentic virulence factors, in accordance with the molecular version of Koch's postulates. 1-3)It has also been well documented that iron and iron-assimilation systems play a crucial role in the pathogenesis of VVS. [4][5][6][7][8] VVS pathogenesis is promoted by the elevated serum iron levels, and crucially requires the assimilation of iron from transferrins by V. vulnificus. 9) V. vulnificus is known to produce two types of siderophores: catechol-and hydroxamate-siderophores. 10) Of these, the catechol-siderophore (called vulnibactin) is known to play the more important role in iron-uptake from transferrins and the virulence of V. vulnificus. [10][11][12][13][14] Expression of the vulnibactin-mediated iron-uptake system is regulated by Fur, a repressor regulating iron uptake. Both the mutation of venB gene encoding an enzyme required for vulnibactin synthesis and the mutation of vuuA gene encoding vulnibactin receptor protein can abolish the ability of V. vulnificus to assimilate iron from transferrins and to grow on holotransferrin (HT).In addition, a metalloprotease (named VvpE) of V. vulnificus has been extensively studied, and is known to exert a variety of biological effects.1-3,15,16) However, the role of VvpE in the pathogenesis of VVS remains unclear, as VvpE-deficient mutants showed comparable or higher virulence than wild type strains in mouse experimental models. [17][18][19] Of the various biological activities of VvpE, its role in facilitating V. vulnificus iron-uptake via the proteolytic cleavage of heme proteins, transferrins, and lactoferrins has attracted some attention. 15,16) However, our previous study demonstrated that an insertional mutation of vvpE gene has no direct effect on iron-assimilation from human transferrins. 20)Bacterial iron-uptake systems are themselves virulence factors in many bacterial pathogens, and are promising vaccine targets.21) Also, iron-chelation is considered a prospective therapeutic means of preventing in vivo bacterial growth. 22) In these regards, it is of considerable importance that bacterial iron-uptake mechanisms be evaluated. However, the roles of vulnibactin and VvpE in V. vulnificus ironuptake from transferrins have been determined using different methods under different experimental conditions. [11][12][13]20) Therefore, we considered that a definitive comparison and reevaluation of the roles of VvpE and vulnibactin is required, i.e., using the ...

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“…V. vulnificus produces both hydroxamate-and phenolate-type siderophores (17). Mutants with impaired catechol (phenolate) siderophore production are less virulent when compared with wild type V. vulnificus (11), and vulnibactin is essential for utilization of transferrin-and lactoferrin-bound iron in vivo (18). Ferric uptake regulator (Fur) 2 is the major iron-responsive transcriptional regulator in Gram-negative bacteria (19).…”

mentioning

confidence: 99%

Iron- and Quorum-sensing Signals Converge on Small Quorum-regulatory RNAs for Coordinated Regulation of Virulence Factors in Vibrio vulnificus

Wen

Kim

2016

Journal of Biological Chemistry

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Vibrio vulnificus is a marine bacterium that causes human infections resulting in high mortality. This pathogen harbors five quorum-regulatory RNAs (Qrr1-5) that affect the expression of pathogenicity genes by modulating the expression of the master regulator SmcR. The qrr genes are activated by phosphorylated LuxO to different degrees; qrr2 is strongly activated; qrr3 and qrr5 are moderately activated, and qrr1 and qrr4 are marginally activated and are the only two that do not respond to cell density-dependent regulation. Qrrs function redundantly to inhibit SmcR at low cell density and fully repress when all five are activated. In this study, we found that iron inhibits qrr expression in three distinct ways. First, the iron-ferric uptake regulator (Fur) complex directly binds to qrr promoter regions, inhibiting LuxO activation by competing with LuxO for cis-acting DNA elements. Second, qrr transcription is repressed by iron independently of Fur. Third, LuxO expression is repressed by iron independently of Fur. We also found that, under ironlimiting conditions, the five Qrrs functioned additively, not redundantly, to repress SmcR, suggesting that cells lacking iron enter a high cell density mode earlier and could thereby modulate expression of virulence factors sooner. This study suggests that iron and quorum sensing, along with their cognate regulatory circuits, are linked together in the coordinated expression of virulence factors.

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Involvement of Vulnibactin and Exocellular Protease in Utilization of Transferrin‐ and Lactoferrin‐Bound Iron by Vibrio vulnificus

Cited by 52 publications

References 28 publications

High growing ability of Vibrio vulnificus biotype 1 is essential for production of a toxic metalloprotease causing systemic diseases in humans

High growing ability of Vibrio vulnificus biotype 1 is essential for production of a toxic metalloprotease causing systemic diseases in humans

Vibrio vulnificus Vulnibactin, But Not Metalloprotease VvpE, Is Essentially Required for Iron-Uptake from Human Holotransferrin

Iron- and Quorum-sensing Signals Converge on Small Quorum-regulatory RNAs for Coordinated Regulation of Virulence Factors in Vibrio vulnificus

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