Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacillus cereus causes a highly fulminant endophthalmitis which usually results in blindness. We previously concluded that hemolysin BL (HBL), a tripartite necrotizing pore-forming toxin, is a probable endophthalmitis virulence factor because it is highly toxic to retinal tissue in vitro and in vivo. We also determined that B. cereus produces additional retinal toxins that might contribute to virulence. Here we fractionated crude B. cereus culture supernatant by anion-exchange chromatography and found that in vitro retinal toxicity was also associated with phosphatidylcholine-preferring phospholipase C (PC-PLC). The pure enzyme also caused retinal necrosis in vivo. We showed that phosphatidylinositol-specific PLC and sphingomyelinase were nontoxic and that two hemolysins, cereolysin O and a novel hemolysin designated hemolysin IV, were marginally toxic in vitro. The histopathology of experimental septic endophthalmitis in rabbits mimicked the pathology produced by pure HBL, and both HBL and PC-PLC were detected at toxic concentrations in infected vitreous fluid. Bacterial cells were first seen associated with the posterior margin of the lens and eventually were located throughout the lens cortex. Detection of collagenase in the vitreous humor suggested that infiltration was facilitated by the breakdown of the protective collagen lens capsule by that enzyme. This work supports our conclusion that HBL contributes to B. cereus virulence and implicates PC-PLC and collagenase as additional virulence factors.
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PMID:Evidence for contribution of tripartite hemolysin BL, phosphatidylcholine-preferring phospholipase C, and collagenase to virulence of Bacillus cereus endophthalmitis. 1094 54

Membrane-damaging toxins are thought to be responsible for the explosive clinical course of Bacillus endophthalmitis. This study analyzed the contribution of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific phospholipase C (PC-PLC) to the pathogenesis of experimental Bacillus endophthalmitis. Isogenic mutants were constructed by insertion of lacZ into Bacillus thuringiensis genes encoding PI-PLC (plcA) and PC-PLC (plcB). Rabbit eyes were injected intravitreally with 2 log(10) CFU of strain BT407 (wild type), the PI-PLC mutant (BTplcA::lacZ), or the PC-PLC mutant (BTplcB::lacZ). The rates of decrease in retinal responses of eyes infected with the isogenic mutants were similar to that of wild type, with all infections resulting in elimination of retinal function by 18 h. Strain BT407 caused a significant increase in the latency of retinal responses at 6 h, but strains BTplcA::lacZ and BTplcB::lacZ did not. All strains elicited significant inflammatory cell influx into the anterior chamber by 12 h. Histologically, eyes infected with each strain were indistinguishable throughout the infection course. In this model, neither PI-PLC nor PC-PLC had an effect on the course or severity of experimental Bacillus endophthalmitis. Alterations in retinal responses early in infection may mark the beginnings of specific photoreceptor or glial cell dysfunction.
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PMID:Contribution of membrane-damaging toxins to Bacillus endophthalmitis pathogenesis. 1222 62

Staphylococcus aureus is a major pathogen of the eye able to infect the tear duct, eyelid, conjunctiva, cornea, anterior and posterior chambers, and the vitreous chamber. Of these infections, those involving the cornea (keratitis) or the inner chambers of the eye (endophthalmitis) are the most threatening because of their potential to cause a loss in visual acuity or even blindness. Each of these ocular sites is protected by the constitutive expression of a variety of antimicrobial factors and these defenses are augmented by a protective host response to the organism. Such infections often involve a predisposing factor that weakens the defenses, such as the use of contact lenses prior to the development of bacterial keratitis or, for endophthalmitis, the trauma caused by cataract surgery or intravitreal injection. The structural carbohydrates of the bacterial surface induce an inflammatory response able to reduce the bacterial load, but contribute to the tissue damage. A variety of bacterial secreted proteins including alpha-toxin, beta-toxin, gamma-toxin, Panton-Valentine leukocidin and other two-component leukocidins mediate tissue damage and contribute to the induction of the inflammatory response. Quantitative animal models of keratitis and endophthalmitis have provided insights into the S. aureus virulence and host factors active in limiting such infections.
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PMID:The Pathogenesis of Staphylococcus aureus Eye Infections. 2932 Apr 51