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

Watanabe, Hirofumi; Miyoshi, Shin Ichi; Kawase, Tomoka; Tomochika, Ken Ichi; Shinoda, Sumió

doi:10.1016/j.micpath.2003.10.001

Cited by 36 publications

(30 citation statements)

References 41 publications

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“…Shinoda and co-workers recently reported that a high growth rate of V. vulnificus in conditions with an abundance of available iron is essential for the efficient production of proteases. 38,39) These results indicate that iron is required for efficient VvpE production, and that VvpE is not required for efficient iron-uptake. However, controversy remains between VvpE production and iron concentration.…”

Section: Discussionmentioning

confidence: 91%

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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Section: Discussionmentioning

confidence: 91%

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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“…Iron seems to enhance the virulence of vibrios. A capsular polysaccharide (CPS) is the primary virulence factor in V. vulnificus pathogenesis (270,422,441). The presence of this factor correlates with the opaque colony phenotype and is thought to play a inflammatory role within the human body.…”

Section: Human Pathogensmentioning

confidence: 99%

“…Bioremediation of polyaromatic hydrocarbons may be carried out by vibrios (161). Vibrios may also be 422 THOMPSON ET AL. MICROBIOL.…”

Section: Perspectives and Exploitationmentioning

confidence: 99%

Biodiversity of Vibrios

Thompson

Iida

Swings

2004

Microbiol Mol Biol Rev

1,062

888

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Vibrios are ubiquitous and abundant in the aquatic environment. A high abundance of vibrios is also detected in tissues and/or organs of various marine algae and animals, e.g., abalones, bivalves, corals, fish, shrimp, sponges, squid, and zooplankton. Vibrios harbour a wealth of diverse genomes as revealed by different genomic techniques including amplified fragment length polymorphism, multilocus sequence typing, repetetive extragenic palindrome PCR, ribotyping, and whole-genome sequencing. The 74 species of this group are distributed among four different families, i.e., Enterovibrionaceae, Photobacteriaceae, Salinivibrionaceae, and Vibrionaceae. Two new genera, i.e., Enterovibrio norvegicus and Grimontia hollisae, and 20 novel species, i.e., Enterovibrio coralii, Photobacterium eurosenbergii, V. brasiliensis, V. chagasii, V. coralliillyticus, V. crassostreae, V. fortis, V. gallicus, V. hepatarius, V. hispanicus, V. kanaloaei, V. neonatus, V. neptunius, V. pomeroyi, V. pacinii, V. rotiferianus, V. superstes, V. tasmaniensis, V. ezurae, and V. xuii, have been described in the last few years. Comparative genome analyses have already revealed a variety of genomic events, including mutations, chromosomal rearrangements, loss of genes by decay or deletion, and gene acquisitions through duplication or horizontal transfer (e.g., in the acquisition of bacteriophages, pathogenicity islands, and super-integrons), that are probably important driving forces in the evolution and speciation of vibrios. Whole-genome sequencing and comparative genomics through the application of, e.g., microarrays will facilitate the investigation of the gene repertoire at the species level. Based on such new genomic information, the taxonomy and the species concept for vibrios will be reviewed in the next years

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“…This means that they are likely to be substrates for protease enzymes that are found in tissue. In particular, extracellular proteases derived from the host cells are found in areas of inflammation such as infections (1,23) and proteases may also be produced by bacteria them-selves as secreted virulence factors involved in tissue invasion (30,47).…”

Section: Vol 50 2006 Photoinactivation With Pei-chlorin(e6) Conjugamentioning

confidence: 99%

Protease-Stable Polycationic Photosensitizer Conjugates between Polyethyleneimine and Chlorin(e6) for Broad-Spectrum Antimicrobial Photoinactivation

Tegos

Anbe

Yang

et al. 2006

Antimicrob Agents Chemother

161

146

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We previously showed that covalent conjugates between poly-L-lysine and chlorin(e6) were efficient photosensitizers (PS) of both gram-positive and gram-negative bacteria. The polycationic molecular constructs increased binding and penetration of the PS into impermeable gram-negative cells. We have now prepared a novel set of second-generation polycationic conjugates between chlorin(e6) and three molecular forms of polyethyleneimine (PEI): a small linear, a small cross-linked, and a large cross-linked molecule. The conjugates were characterized by high-pressure liquid chromatography and tested for their ability to kill a panel of pathogenic microorganisms, the gram-positive Staphylococcus aureus and Streptococcus pyogenes, the gramnegative Escherichia coli and Pseudomonas aeruginosa, and the yeast Candida albicans, after exposure to low levels of red light. The large cross-linked molecule efficiently killed all organisms, while the linear conjugate killed gram-positive bacteria and C. albicans. The small cross-linked conjugate was the least efficient antimicrobial PS and its remarkably low activity could not be explained by reduced photochemical quantum yield or reduced cellular uptake. In contrast to polylysine conjugates, the PEI conjugates were resistant to degradation by proteases such as trypsin that hydrolyze lysine-lysine peptide bonds, The advantage of protease stability combined with the ready availability of PEI suggests these molecules may be superior to polylysine-PS conjugates for photodynamic therapy of localized infections.Photodynamic therapy (PDT) employs a nontoxic dye termed a photosensitizer (PS) and low-intensity visible light, which in the presence of oxygen produce cytotoxic species (4-6). PDT has the advantage of dual selectivity in that the PS can be targeted to its destination cell or tissue, and in addition the illumination can be spatially directed to the lesion. PDT was originally discovered over 100 years ago by its effect on microorganisms (35) but since then has been principally developed as a treatment for cancer (11) and age-related macular degeneration (3).Because of the well-known increase in multiantibiotic resistance among pathogenic microbes of all classes, PDT has attracted attention as a possible treatment for localized infections (9, 14, 46). It is known that gram-negative bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity for gram-positive species (29) and that PS bearing a cationic charge (33) or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing of gram-negative organisms (29).In 1997 our laboratory formed the hypothesis that by covalently conjugating a suitable PS such as chlorin(e6) (ce6) to a poly-L-lysine (pL) chain, a bacterially targeted PS delivery vehicle could be constructed that would efficiently inactivate both gram-positive and gram-negative species (42). Because the resulting polycationic entity is a macromolecule, it is taken up by mammalian cells by th...

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

Cited by 36 publications

References 41 publications

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

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

Biodiversity of Vibrios

Protease-Stable Polycationic Photosensitizer Conjugates between Polyethyleneimine and Chlorin(e6) for Broad-Spectrum Antimicrobial Photoinactivation

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