A Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin

ABSTRACT Intraocular infections are a potentially blinding complication of common ocular surgeries and traumatic eye injuries. Bacterial toxins synthesized in the eye can damage intraocular tissue, often resulting in poor visual outcomes. Enteroccocus faecalis causes blinding infections and is respo...

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Autores principales:	Austin L. LaGrow, Phillip S. Coburn, Frederick C. Miller, Craig Land, Salai Madhumathi Parkunan, Brian T. Luk, Weiwei Gao, Liangfang Zhang, Michelle C. Callegan
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Enterococcus cytolysin cytotoxins endophthalmitis eye infection nanoparticle Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/82aadfce2f2a47458f3780d1003dfb2b
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id	oai:doaj.org-article:82aadfce2f2a47458f3780d1003dfb2b
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	Enterococcus cytolysin cytotoxins endophthalmitis eye infection nanoparticle Microbiology QR1-502
spellingShingle	Enterococcus cytolysin cytotoxins endophthalmitis eye infection nanoparticle Microbiology QR1-502 Austin L. LaGrow Phillip S. Coburn Frederick C. Miller Craig Land Salai Madhumathi Parkunan Brian T. Luk Weiwei Gao Liangfang Zhang Michelle C. Callegan A Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin
description	ABSTRACT Intraocular infections are a potentially blinding complication of common ocular surgeries and traumatic eye injuries. Bacterial toxins synthesized in the eye can damage intraocular tissue, often resulting in poor visual outcomes. Enteroccocus faecalis causes blinding infections and is responsible for 8 to 17% of postoperative endophthalmitis cases. These infections are increasingly difficult to treat due to the emergence of multidrug-resistant strains. Virulent E. faecalis isolates secrete a pore-forming bicomponent cytolysin that contributes to retinal tissue damage during endophthalmitis. We hypothesized that a biomimetic nanosponge, which mimics erythrocytes, might adsorb subunits of the cytolysin and reduce retinal damage, protecting vision. To test the efficacy of nanosponges in neutralizing the cytolysin in vitro, hemoglobin release assays were performed on culture supernatants from cytolysin-producing E. faecalis with and without preincubation with nanosponges. Treatment with nanosponges for 30 min reduced hemolytic activity by ~70%. To determine whether nanosponges could neutralize the cytolysin in vivo, electroretinography was performed on mice 24 h after intravitreal injection with cytolysin-containing supernatants treated with nanosponges. Pretreatment of cytolysin-containing supernatants with nanosponges increased the A-wave retention from 12.2% to 65.5% and increased the B-wave retention from 21.0% to 77.0%. Histology revealed that in nanosponge-treated eyes, retinas remained intact and attached, with little to no damage. Rabbit nanosponges were also nontoxic and noninflammatory when injected into mouse eyes. In an experimental murine model of E. faecalis endophthalmitis, injection of nanosponges into the vitreous 6 h after infection with a wild-type cytolysin-producing strain increased A-wave retention from 5.9% to 31% and increased B-wave retention from 12.6% to 27.8%. Together, these results demonstrated that biomimetic nanosponges neutralized cytolysin activity and protected the retinas from damage. These results suggest that this novel strategy might also protect eyes from the activities of pore-forming toxins of other virulent ocular bacterial pathogens. IMPORTANCE Endophthalmitis is a serious, potentially blinding infection that can result in vision loss, leaving a patient with only the ability to count fingers, or it may require enucleation of the globe. The incidence of postoperative endophthalmitis has markedly increased over the past 2 decades, paralleling the rise in ocular surgeries and intravitreal therapies. E. faecalis is a leading cause of infection following ocular procedures, and such infections are increasingly difficult to treat due to multidrug resistance. Cytolysin is the primary virulence factor responsible for retinal tissue damage in E. faecalis eye infections. Treatment of these infections with antibiotics alone does not impede ocular damage and loss of visual function. Pore-forming toxins (PFTs) have been established as major virulence factors in endophthalmitis caused by several bacterial species. These facts establish a critical need for a novel therapy to neutralize bacterial PFTs such as cytolysin. Here, we demonstrate that biomimetic nanosponges neutralize cytolysin, protect the retina, preserve vision, and may provide an adjunct detoxification therapy for bacterial infections.
format	article
author	Austin L. LaGrow Phillip S. Coburn Frederick C. Miller Craig Land Salai Madhumathi Parkunan Brian T. Luk Weiwei Gao Liangfang Zhang Michelle C. Callegan
author_facet	Austin L. LaGrow Phillip S. Coburn Frederick C. Miller Craig Land Salai Madhumathi Parkunan Brian T. Luk Weiwei Gao Liangfang Zhang Michelle C. Callegan
author_sort	Austin L. LaGrow
title	A Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin
title_short	A Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin
title_full	A Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin
title_fullStr	A Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin
title_full_unstemmed	A Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin
title_sort	novel biomimetic nanosponge protects the retina from the <named-content content-type="genus-species">enterococcus faecalis</named-content> cytolysin
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/82aadfce2f2a47458f3780d1003dfb2b
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spelling	oai:doaj.org-article:82aadfce2f2a47458f3780d1003dfb2b2021-11-15T15:21:51ZA Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin10.1128/mSphere.00335-172379-5042https://doaj.org/article/82aadfce2f2a47458f3780d1003dfb2b2017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00335-17https://doaj.org/toc/2379-5042ABSTRACT Intraocular infections are a potentially blinding complication of common ocular surgeries and traumatic eye injuries. Bacterial toxins synthesized in the eye can damage intraocular tissue, often resulting in poor visual outcomes. Enteroccocus faecalis causes blinding infections and is responsible for 8 to 17% of postoperative endophthalmitis cases. These infections are increasingly difficult to treat due to the emergence of multidrug-resistant strains. Virulent E. faecalis isolates secrete a pore-forming bicomponent cytolysin that contributes to retinal tissue damage during endophthalmitis. We hypothesized that a biomimetic nanosponge, which mimics erythrocytes, might adsorb subunits of the cytolysin and reduce retinal damage, protecting vision. To test the efficacy of nanosponges in neutralizing the cytolysin in vitro, hemoglobin release assays were performed on culture supernatants from cytolysin-producing E. faecalis with and without preincubation with nanosponges. Treatment with nanosponges for 30 min reduced hemolytic activity by ~70%. To determine whether nanosponges could neutralize the cytolysin in vivo, electroretinography was performed on mice 24 h after intravitreal injection with cytolysin-containing supernatants treated with nanosponges. Pretreatment of cytolysin-containing supernatants with nanosponges increased the A-wave retention from 12.2% to 65.5% and increased the B-wave retention from 21.0% to 77.0%. Histology revealed that in nanosponge-treated eyes, retinas remained intact and attached, with little to no damage. Rabbit nanosponges were also nontoxic and noninflammatory when injected into mouse eyes. In an experimental murine model of E. faecalis endophthalmitis, injection of nanosponges into the vitreous 6 h after infection with a wild-type cytolysin-producing strain increased A-wave retention from 5.9% to 31% and increased B-wave retention from 12.6% to 27.8%. Together, these results demonstrated that biomimetic nanosponges neutralized cytolysin activity and protected the retinas from damage. These results suggest that this novel strategy might also protect eyes from the activities of pore-forming toxins of other virulent ocular bacterial pathogens. IMPORTANCE Endophthalmitis is a serious, potentially blinding infection that can result in vision loss, leaving a patient with only the ability to count fingers, or it may require enucleation of the globe. The incidence of postoperative endophthalmitis has markedly increased over the past 2 decades, paralleling the rise in ocular surgeries and intravitreal therapies. E. faecalis is a leading cause of infection following ocular procedures, and such infections are increasingly difficult to treat due to multidrug resistance. Cytolysin is the primary virulence factor responsible for retinal tissue damage in E. faecalis eye infections. Treatment of these infections with antibiotics alone does not impede ocular damage and loss of visual function. Pore-forming toxins (PFTs) have been established as major virulence factors in endophthalmitis caused by several bacterial species. These facts establish a critical need for a novel therapy to neutralize bacterial PFTs such as cytolysin. Here, we demonstrate that biomimetic nanosponges neutralize cytolysin, protect the retina, preserve vision, and may provide an adjunct detoxification therapy for bacterial infections.Austin L. LaGrowPhillip S. CoburnFrederick C. MillerCraig LandSalai Madhumathi ParkunanBrian T. LukWeiwei GaoLiangfang ZhangMichelle C. CalleganAmerican Society for MicrobiologyarticleEnterococcuscytolysincytotoxinsendophthalmitiseye infectionnanoparticleMicrobiologyQR1-502ENmSphere, Vol 2, Iss 6 (2017)

A Novel Biomimetic Nanosponge Protects the Retina from the <named-content content-type="genus-species">Enterococcus faecalis</named-content> Cytolysin

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