Identification and Potency of Cyclodextrin-Lipid Inhibitors of<i>Staphylococcus aureus</i>α-Toxin

Weeks, Anastasia C.; Balzli, Charles L.; Caballero, Armando R.; Tang, Aihua; O’Callaghan, Richard J.

doi:10.3109/02713683.2011.624669

Cited by 9 publications

(6 citation statements)

References 26 publications

(37 reference statements)

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“…Because of the potency of alpha-toxin in the cornea, efforts have been made to inhibit its action on the cornea. Combinations of lipid with cyclodextrin have been shown to inhibit alpha-toxin mediated lysis of erythrocytes and one such inhibitor containing cholesterol has been shown to reduce the severity of S. aureus keratitis in the rabbit eye [ 90 , 91 ]. Antibody to alpha-toxin neutralizes the toxin in vitro and prior immunization with the alpha-toxin toxoid protects the rabbit cornea from the severe effects of the toxin during keratitis [ 77 , 92 ].…”

Section: Keratitismentioning

confidence: 99%

The Pathogenesis of Staphylococcus aureus Eye Infections

O’Callaghan

2018

Pathogens

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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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Section: Keratitismentioning

confidence: 99%

The Pathogenesis of Staphylococcus aureus Eye Infections

O’Callaghan

2018

Pathogens

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“…There was a small effect on antimicrobial activity of dissolving the fimbrolides in cyclodextrin/ sodium acetate solution; the zone of inhibition on the agar plate changed from 5.5 mm to 5.0 mm. Previous studies have shown that cyclodextrins alone do not affect α-toxin production [30]. There were no clinical changes in the mouse cornea or conjunctiva after repeated instillation of the cyclodextrin/sodium acetate solution.…”

Section: Resultsmentioning

confidence: 62%

“…After growth, cells were removed by centrifugation (5,000 g 10 mins) and the supernatants removed and filtered through 0.22 µm filters. Citrated rabbit erythrocytes were purchased from Bioreclamation IVT (NY, USA), washed in PBS (8 g/l NaCl, 0.2 g/l KCl, 1.15 g/l Na 2 HPO 4 , 0.2 g/l KH 2 PO 4 , pH 7.3) and resuspended in PBS and added to wells of a 96 well micro titer plate at approximately 10 7 erythrocytes/well [30]. Bacterial supernatants were added and the mixtures allowed incubating at 37 °C for 1 hour.…”

Section: Effect Of Fimbrolide On Production Of α-Toxinmentioning

confidence: 99%

Treatment of Staphylococcus Aureus with Antibiotic and Quorum-Sensing Inhibitor Combinations Reduces Severity of Keratitis

2017

J Ocular Biol

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To examine whether treatment with ciprofloxacin and fimbrolides improves the outcome of Staphylococcus aureus keratitis.Methods: A S. aureus strain was tested for the minimum inhibitory concentration (MIC) of ciprofloxacin and fimbrolides, and whether they had synergistic antimicrobial activity. The effect of fimbrolides on production of α-toxin was measured after growth at sub-MIC and testing supernatants for hemolysis. Cytotoxicity of the fimbrolides was measured by adding increasing concentrations to corneal epithelial cells and measuring release of lactate dehydrogenase. Ten hours after scratching corneas of mice and applying bacteria, treatment was initiated with vehicle, ciprofloxacin, fimbrolide, or a combination of ciprofloxacin and fimbrolide. The number of infecting S. aureus cells was measured after 6 hours treatment, and clinical responses were recorded (maximum score 20). Results:The MIC of the fimbrolides was 6.25-12.5 μM and growth in fimbrolides reduced production of α-toxin by > 90%. Fimbrolides were only cytotoxic at ≥ 25 μM. Treatment of keratitis with ciprofloxacin significantly (p < 0.05) reduced numbers of S. aureus in corneas. Although there was minimal synergism between the two antimicrobials in vitro and treatment with the fimbrolide/ciprofloxacin combination in vivo did not significantly reduce numbers of S. aureus, there was a significantly reduced clinical score (by > 45%; p < 0.05) of the combination compared to single application of antimicrobials or vehicle control (average 4.25 ± 0.35). Conclusion:Application of non-toxic concentrations of quorum-sensing inhibitor fimbrolides in combination with ciprofloxacin reduce the numbers infecting bacteria to the same extent as ciprofloxacin alone, but also significantly improved the clinical outcome of S. aureus keratitis. Fimbrolides may be useful adjunct agents to treat keratitis.

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“…The virulence-targeted therapies include monoclonal antibodies, chemical inhibitors, antisera, and molecularly imprinted polymers . These existing detoxification strategies mainly aim to target the single-molecular structure of the bacterial toxins.…”

Section: Cell Membrane-coated Nanoparticles For the Management Of Bac...mentioning

confidence: 99%

Cell Membrane-Coated Nanoparticles for Management of Infectious Diseases: A Review

Sun

Yang

et al. 2022

Ind. Eng. Chem. Res.

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Infectious diseases have emerged as leading threats to global healthcare, such as bacterial and viral infections. Major challenges in combating these infectious diseases are the emergence of adverse effects during the long-term use of anti-infectious drugs and the increasing prevalence of drug resistance. Cell membrane-coated nanoparticles have great potential in the prevention and therapy of infectious diseases. This promising therapeutic strategy is to employ cell membrane-based nanoparticles as a decoy to detain pathogenic microbes, a drug delivery platform, and an immunogenicity complex. Herein, the accelerating progression of biomimetic cell membrane-coated nanoparticles for the management of various infectious diseases is highlighted. We also discuss the challenges and the further application of cell membrane-coated nanoparticles in the view of clinical translation for combating infectious diseases. With a better understanding of the bioinspired camouflaged strategy, we anticipate that the use of cell membrane-coated nanoparticles will continue to grow and promote their applications in infectious diseases.

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Identification and Potency of Cyclodextrin-Lipid Inhibitors ofStaphylococcus aureusα-Toxin

Cited by 9 publications

References 26 publications

The Pathogenesis of Staphylococcus aureus Eye Infections

The Pathogenesis of Staphylococcus aureus Eye Infections

Treatment of Staphylococcus Aureus with Antibiotic and Quorum-Sensing Inhibitor Combinations Reduces Severity of Keratitis

Cell Membrane-Coated Nanoparticles for Management of Infectious Diseases: A Review

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