Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vibrio tubiashii, a pathogen of shellfish larvae and juveniles, produces several extracellular products. Here, we document that culture supernatants of several marine Vibrio species showed toxicity to oyster larvae. Treatment of these supernatants with EDTA not only severely diminished proteolytic activities, but also dramatically reduced toxicity to the larvae. Culture supernatants of metalloprotease-deficient mutants of V. tubiashii, V. cholerae, and V. splendidus were impaired in their ability to cause larval death compared to the wild type strains. Culture supernatants of Pseudomonas aeruginosa, known to contain several secreted proteases, showed virtually no toxicity to oyster larvae. Purified V. tubiashii protease A (VtpA), but not the prototype metalloprotease, thermolysin from Bacillus thermoproteolyticus, was highly toxic to the larvae. In addition, toxicity of purified VtpA was much greater for 6-d-old oyster larvae than for 16-d-old larvae. Together, these results indicated that culture supernatants of a variety of Vibrio species are highly toxic to oyster larvae and that the production of a metalloprotease is required for this effect. We propose that there are, as yet uncharacterized, specific substrates contained in larval tissue that are degraded by VtpA as well as certain homologous metalloproteases produced by other marine Vibrio species which, in turn, may contribute to vibriosis.
 ...
PMID:Virulence of metalloproteases produced by Vibrio species on Pacific oyster Crassostrea gigas larvae. 1969 72

Vibrio vulnificus and Vibrio cholerae are Gram-negative pathogens that cause serious infectious disease in humans. The beta form of pro-IL-1 is thought to be involved in inflammatory responses and disease development during infection with these pathogens, but the mechanism of beta form of pro-IL-1 production remains poorly defined. In this study, we demonstrate that infection of mouse macrophages with two pathogenic Vibrio triggers the activation of caspase-1 via the NLRP3 inflammasome. Activation of the NLRP3 inflammasome was mediated by hemolysins and multifunctional repeat-in-toxins produced by the pathogenic bacteria. NLRP3 activation in response to V. vulnificus infection required NF-kappaB activation, which was mediated via TLR signaling. V. cholerae-induced NLRP3 activation also required NF-kappaB activation but was independent of TLR stimulation. Studies with purified V. cholerae hemolysin revealed that toxin-stimulated NLRP3 activation was induced by TLR and nucleotide-binding oligomerization domain 1/2 ligand-mediated NF-kappaB activation. Our results identify the NLRP3 inflammasome as a sensor of Vibrio infections through the action of bacterial cytotoxins and differential activation of innate signaling pathways acting upstream of NF-kappaB.
 ...
PMID:Pathogenic Vibrio activate NLRP3 inflammasome via cytotoxins and TLR/nucleotide-binding oligomerization domain-mediated NF-kappa B signaling. 2034 25