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Dr. Michelle C. Callegan
Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd., DMEI-PA418 Oklahoma City, OK 73104, USA

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0 endophthalmitis
0 keratitis
0 bacterial toxins
0 Nanotherapeutics
0 Bacterial ocular infections

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endophthalmitis
keratitis
Ocular inflammation
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Bacterial ocular infections

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Journal article
Published: 07 June 2021 in Infection and Immunity
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Endophthalmitis is a devastating infection that can cause blindness. Over half of Bacillus endophthalmitis cases result in significant loss of useful vision. Bacillus produces many virulence factors that may contribute to retinal damage and robust inflammation. We analyzed Bacillus immune inhibitor A (InhA) metalloproteases in the context of this disease, hypothesizing that InhAs contribute to Bacillus intraocular virulence and inflammation. We analyzed phenotypes and infectivity of wild type (WT), InhA1-deficient (Δ inhA1 ), InhA2-deficient (Δ inhA2 ), or InhA1, A2, and A3-deficient (Δ inhA1-3 ) Bacillus thuringiensis . In vitro analysis of growth, proteolysis, and cytotoxicity were compared. WT and InhA mutants were similarly cytotoxic to retinal cells. Mutants Δ inhA1 and Δ inhA2 entered log phase growth earlier than WT. Proteolysis by the Δ inhA1-3 mutant was decreased, but this strain grew similar to WT in vitro . Experimental endophthalmitis was initiated by intravitreally infecting C57BL/6J mice with 200 CFU of B. thuringiensis WT or InhA mutants. Eyes were analyzed for intraocular Bacillus and myeloperoxidase concentrations, retinal function loss, and gross histological changes. Eyes infected with Δ inhA1 or Δ inhA2 strains contained greater numbers of bacteria than eyes infected with WT throughout the infection course. Eyes infected with single mutants had inflammation and retinal function loss similar to eyes infected with WT strain. Eyes infected with Δ inhA1-3 cleared the infection. RT-PCR results suggested that there may be compensatory expression of the other InhAs in the single InhA mutant. These results indicate that together, the InhA metalloproteases contribute to the severity of infection and inflammation in Bacillus endophthalmitis.

ACS Style

Erin Livingston; Huzzatul Mursalin; Phillip S. Coburn; Roger Astley; Frederick C. Miller; Omar Amayem; Didier Lereclus; Michelle C. Callegan. Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis. Infection and Immunity 2021, IAI0020121 .

AMA Style

Erin Livingston, Huzzatul Mursalin, Phillip S. Coburn, Roger Astley, Frederick C. Miller, Omar Amayem, Didier Lereclus, Michelle C. Callegan. Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis. Infection and Immunity. 2021; ():IAI0020121.

Chicago/Turabian Style

Erin Livingston; Huzzatul Mursalin; Phillip S. Coburn; Roger Astley; Frederick C. Miller; Omar Amayem; Didier Lereclus; Michelle C. Callegan. 2021. "Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis." Infection and Immunity , no. : IAI0020121.

Video audio media
Published: 06 February 2021 in Journal of Visualized Experiments
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Intraocular bacterial infections are a danger to the vision. Researchers use animal models to investigate the host and bacterial factors and immune response pathways associated with infection to identify viable therapeutic targets and to test drugs to prevent blindness. The intravitreal injection technique is used to inject organisms, drugs, or other substances directly into the vitreous cavity in the posterior segment of the eye. Here, we demonstrated this injection technique to initiate infection in the mouse eye and the technique of quantifying intraocular bacteria. Bacillus cereus was grown in brain heart infusion liquid media for 18 hours and resuspended to a concentration 100 colony forming units (CFU)/0.5 µL. A C57BL/6J mouse was anesthetized using a combination of ketamine and xylazine. Using a picoliter microinjector and glass capillary needles, 0.5 µL of the Bacillus suspension was injected into the mid vitreous of the mouse eye. The contralateral control eye was either injected with sterile media (surgical control) or was not injected (absolute control). At 10 hours post infection, mice were euthanized, and eyes were harvested using sterile surgical tweezers and placed into a tube containing 400 µL sterile PBS and 1 mm sterile glass beads. For ELISAs or myeloperoxidase assays, proteinase inhibitor was added to the tubes. For RNA extraction, the appropriate lysis buffer was added. Eyes were homogenized in a tissue homogenizer for 1-2 minutes. Homogenates were serially diluted 10-fold in PBS and track diluted onto agar plates. The remainder of the homogenates were stored at -80 °C for additional assays. Plates were incubated for 24 hours and CFU per eye was quantified. These techniques result in reproducible infections in mouse eyes and facilitate quantitation of viable bacteria, the host immune response, and omics of host and bacterial gene expression.

ACS Style

Huzzatul Mursalin; Erin Livingston; Phillip S. Coburn; Frederick C. Miller; Roger Astley; Michelle C. Callegan. Intravitreal Injection and Quantitation of Infection Parameters in a Mouse Model of Bacterial Endophthalmitis. Journal of Visualized Experiments 2021, e61749 .

AMA Style

Huzzatul Mursalin, Erin Livingston, Phillip S. Coburn, Frederick C. Miller, Roger Astley, Michelle C. Callegan. Intravitreal Injection and Quantitation of Infection Parameters in a Mouse Model of Bacterial Endophthalmitis. Journal of Visualized Experiments. 2021; (168):e61749.

Chicago/Turabian Style

Huzzatul Mursalin; Erin Livingston; Phillip S. Coburn; Frederick C. Miller; Roger Astley; Michelle C. Callegan. 2021. "Intravitreal Injection and Quantitation of Infection Parameters in a Mouse Model of Bacterial Endophthalmitis." Journal of Visualized Experiments , no. 168: e61749.

Immunology and microbiology
Published: 02 November 2020 in Investigative Opthalmology & Visual Science
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Purpose: To explore the consequences of innate interference on intraocular inflammatory responses during Bacillus endophthalmitis. Methods: Bacillus endophthalmitis was induced in mice. Innate immune pathway activation was interfered by injecting S layer protein-deficient (∆slpA) B. thuringiensis or by treating wild-type (WT)–infected mice with a TLR2/4 inhibitor (WT+OxPAPC). At 10 hours postinfection, eyes were harvested and RNA was purified. A NanoString murine inflammation panel was used to compare gene expression in WT-infected, WT+OxPAPC, ∆slpA-infected, and uninfected eyes. Results: In WT-infected eyes, 56% of genes were significantly upregulated compared to uninfected controls. Compared to WT-infected eyes, the expression of 27% and 50% of genes were significantly reduced in WT+OxPAPC and ∆slpA-infected eyes, respectively. Expression of 61 genes that were upregulated in WT-infected eyes was decreased in WT+OxPAPC and ∆slpA-infected eyes. Innate interference resulted in blunted expression of complement factors (C3, Cfb, and C6) and several innate pathway genes (TLRs 2, 4, 6, and 8, MyD88, Nod2, Nlrp3, NF-κB, STAT3, RelA, RelB, and Ptgs2). Innate interference also reduced the expression of several inflammatory cytokines (CSF2, CSF3, IL-6, IL-1β, IL-1α, TNFα, IL-23α, TGFβ1, and IL-12β) and chemokines (CCL2, CCL3, and CXCLs 1, 2, 3, 5, 9, and 10). All of the aforementioned genes were significantly upregulated in WT-infected eyes. Conclusions: These results suggest that interfering with innate activation significantly reduced the intraocular inflammatory response in Bacillus endophthalmitis. This positive clinical outcome could be a strategy for anti-inflammatory therapy of an infection typically refractory to corticosteroid treatment.

ACS Style

Huzzatul Mursalin; Phillip S. Coburn; Frederick C. Miller; Erin T. Livingston; Roger Astley; Michelle C. Callegan. Innate Immune Interference Attenuates Inflammation InBacillusEndophthalmitis. Investigative Opthalmology & Visual Science 2020, 61, 17 -17.

AMA Style

Huzzatul Mursalin, Phillip S. Coburn, Frederick C. Miller, Erin T. Livingston, Roger Astley, Michelle C. Callegan. Innate Immune Interference Attenuates Inflammation InBacillusEndophthalmitis. Investigative Opthalmology & Visual Science. 2020; 61 (13):17-17.

Chicago/Turabian Style

Huzzatul Mursalin; Phillip S. Coburn; Frederick C. Miller; Erin T. Livingston; Roger Astley; Michelle C. Callegan. 2020. "Innate Immune Interference Attenuates Inflammation InBacillusEndophthalmitis." Investigative Opthalmology & Visual Science 61, no. 13: 17-17.

Preprint content
Published: 06 July 2020
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Bacterial endophthalmitis is a devastating infection that can cause blindness following the introduction of organisms into the posterior segment of the eye. Over half of Bacillus endophthalmitis cases result in significant loss of useful vision. Often, these eyes have to be enucleated. Bacillus produces many virulence factors in the eye that may contribute to retinal damage and robust inflammation. This study analyzed Bacillus immune inhibitor A (InhA) metalloproteases, which digest extracellular matrix, tight junction proteins, and antimicrobial proteins. We hypothesized that InhAs contribute to Bacillus intraocular virulence and inflammation. We analyzed phenotypes and infectivity of wild type (WT), InhA1-deficient (ΔinhA1), InhA2-deficient (ΔinhA2), or InhA1, A2, and A3-deficient (ΔinhA1-3) Bacillus thuringiensis. In vitro analysis of growth, proteolysis, and cytotoxicity were compared between B. thuringiensis strains. WT and InhA mutants were similarly cytotoxic to retinal cells. Mutant ΔinhA1 and ΔinhA2 entered log phase growth earlier than WT. Proteolysis of the ΔinhA1-3 mutant was decreased, but this strain grew similar to WT in vitro. Experimental endophthalmitis was initiated by intravitreally infecting C57BL/6J mice with 200 CFU of B. thuringiensis WT or InhA mutants. Intraocular Bacillus and retinal function loss were quantified. Intraocular myeloperoxidase concentrations were quantified and histology was analyzed. Eyes infected with ΔinhA1 or ΔinhA2 strains contained greater numbers of bacteria than eyes infected with WT throughout the course of infection. Eyes infected with single mutants had inflammation and retinal function loss similar to eyes infected with WT strain. Eyes infected with ΔinhA1-3 cleared the infection, with less retinal function loss and inflammation compared to eyes infected with the WT strain. RT-PCR results suggested that single InhA mutant results may be explained by compensatory expression of the other InhAs in these mutants. These results indicate that together, the InhA metalloproteases contribute to the severity of infection and inflammation in Bacillus endophthalmitis.

ACS Style

Erin T Livingston; Huzzatul Mursalin; Phillip S Coburn; Roger Astley; Frederick C Miller; Omar Amayem; Didier Lereclus; Michelle Callegan. Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis. 2020, 1 .

AMA Style

Erin T Livingston, Huzzatul Mursalin, Phillip S Coburn, Roger Astley, Frederick C Miller, Omar Amayem, Didier Lereclus, Michelle Callegan. Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis. . 2020; ():1.

Chicago/Turabian Style

Erin T Livingston; Huzzatul Mursalin; Phillip S Coburn; Roger Astley; Frederick C Miller; Omar Amayem; Didier Lereclus; Michelle Callegan. 2020. "Immune Inhibitor A Metalloproteases Contribute to Virulence in Bacillus Endophthalmitis." , no. : 1.

Preprint content
Published: 02 July 2020
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Bacillus cereus is recognized as a causative agent of gastrointestinal syndromes, but can also cause a devastating form of intraocular infection known as endophthalmitis. We have previously reported that the PlcR/PapR master virulence factor regulator system regulates intraocular virulence, and that the S-layer protein (SlpA) contributes to the severity of B. cereus endophthalmitis. To begin to better understand the role of other B. cereus virulence genes in endophthalmitis, expression levels of a subset of factors was measured at the midpoint of disease progression in a murine model of experimental endophthalmitis by RNA-Seq. Several cytolytic toxins were expressed at significantly higher levels in vivo than in BHI. The virulence regulators codY, gntR, and nprR were also expressed in vivo. However, at this timepoint, plcR/papR was not detectable, we previously reported that a B. cereus mutant deficient in PlcR was attenuated in the eye. The motility-related genes fla, fliF, and motB, and the chemotaxis-related gene cheA were detected during infection. We have shown previously that motility and chemotaxis phenotypes are important in B. cereus endophthalmitis. The sodA2 variant of manganese superoxide dismutase was the most highly expression gene in vivo, suggesting that this gene is criticial for intraocular survival, potentially through inhibition of neutrophil activity. Expression of the surface layer protein gene, slpA, an activator of Toll-like receptors (TLR)-2 and -4, and a potent contributor to intraocular inflammation and disease severvity, was also detected during infection, albeit at low levels. In summary, genes expressed in a mouse model of Bacillus endophthalmitis might prove to play crucial roles in the unique virulence of B. cereus endophthalmitis, and serve as candidates for novel therapies designed attenuate the severity of this often blinding infection.

ACS Style

Phillip S Coburn; Frederick C Miller; Morgan A Enty; Craig Land; Austin L LaGrow; Huzzatul Mursalin; Michelle C Callegan. The Bacillus Virulome in Endophthalmitis. 2020, 1 .

AMA Style

Phillip S Coburn, Frederick C Miller, Morgan A Enty, Craig Land, Austin L LaGrow, Huzzatul Mursalin, Michelle C Callegan. The Bacillus Virulome in Endophthalmitis. . 2020; ():1.

Chicago/Turabian Style

Phillip S Coburn; Frederick C Miller; Morgan A Enty; Craig Land; Austin L LaGrow; Huzzatul Mursalin; Michelle C Callegan. 2020. "The Bacillus Virulome in Endophthalmitis." , no. : 1.

Preprint content
Published: 10 June 2020 in bioRxiv
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PURPOSE Bacillusendophthalmitis is a sight-threatening bacterial infection that sometimes requires enucleation. Inflammation in this disease is driven by activation of innate Toll-like receptor (TLR) pathways. Here, we explored the consequences of innate immune interference on intraocular inflammatory responses duringBacillusendophthalmitis. METHODS Endophthalmitis was induced in mice by injecting 100 CFUBacillus thuringiensisin to the mid-vitreous. We interfered with activation of the TLR2 and TLR4 pathways by 1) injecting a group of mice with S layer protein-deficient (ΔslpA)B. thuringiensisor 2) injecting a group of wild type (WT)-infected mice with a TLR2/4 inhibitor, oxidized phospholipid (OxPAPC). At 10 hours postinfection, infected eyes were removed and total RNA was purified. mRNA expression was then analyzed by NanoString using a murine inflammation panel. We compared findings with expression data from eyes infected with eyes injected with WTB. thuringiensis, eyes injected with OxPAPC alone, and uninfected eyes. RESULTS Interference of TLR2 and TLR4 pathways resulted in differential expression of mouse inflammatory genes compared to expression in WT-infected eyes. In WT-infected eyes, 56% of genes were significantly upregulated compared to that of uninfected controls. However, compared to WT-infected eyes, the expression of 27% and 50% of genes were significantly reduced in WT+OxPAPC and ΔslpA-infected eyes, respectively. The expression of 61 genes which were significantly upregulated in WT-infected eyes was decreased in WT+OxPAPC or ΔslpA-infected eyes. Interference with activation of the TLR2 and TLR4 pathways resulted in blunted expression of complement factors (C3, Cfb, and C6) and several innate genes such as TLR2, TLR4, TLR6, TLR8, MyD88, Nod2, Nlrp3, NF-κB, STAT3, RelA, RelB, and Ptgs2. Interference with activation of the TLR2 and TLR4 pathways also reduced the expression of several inflammatory cytokines such as CSF3, IL-6, IL-1β, CSF2, IL-1α, TNFα, IL-23α, TGFβ1, and IL-12β and chemokines CCL2, CCl3, CXCL1, CXCL2, CXCL3, CXCL5, CXCL9, and CXCL10. All of the aforementioned genes were significantly upregulated in WT-infected eyes. CONCLUSIONS These results suggest that interfering with the activation of innate immune pathways duringBacillusendophthalmitis significantly reduced the intraocular inflammatory response. This positive clinical outcome could be a strategy for anti-inflammatory therapy of an infection typically refractory to corticosteroid treatment.

ACS Style

Huzzatul Mursalin; Phillip S. Coburn; Frederick C. Miller; Erin Livingston; Roger Astley; Michelle C. Callegan. INNATE IMMUNE INTERFERENCE ATTENUATES INFLAMMATION INBACILLUSENDOPHTHALMITIS. bioRxiv 2020, 1 .

AMA Style

Huzzatul Mursalin, Phillip S. Coburn, Frederick C. Miller, Erin Livingston, Roger Astley, Michelle C. Callegan. INNATE IMMUNE INTERFERENCE ATTENUATES INFLAMMATION INBACILLUSENDOPHTHALMITIS. bioRxiv. 2020; ():1.

Chicago/Turabian Style

Huzzatul Mursalin; Phillip S. Coburn; Frederick C. Miller; Erin Livingston; Roger Astley; Michelle C. Callegan. 2020. "INNATE IMMUNE INTERFERENCE ATTENUATES INFLAMMATION INBACILLUSENDOPHTHALMITIS." bioRxiv , no. : 1.

Journal article
Published: 22 April 2020 in Microorganisms
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Bacillus cereus produces many factors linked to pathogenesis and is recognized for causing gastrointestinal toxemia and infections. B. cereus also causes a fulminant and often blinding intraocular infection called endophthalmitis. We reported that the PlcR/PapR system regulates intraocular virulence, but the specific factors that contribute to B. cereus virulence in the eye remain elusive. Here, we compared gene expression in ex vivo vitreous humor with expression in Luria Bertani (LB) and Brain Heart Infusion (BHI) broth by RNA-Seq. The expression of several cytolytic toxins in vitreous was less than or similar to levels observed in BHI or LB. Regulators of virulence genes, including PlcR/PapR, were expressed in vitreous. PlcR/PapR was expressed at low levels, though we reported that PlcR-deficient B. cereus was attenuated in the eye. Chemotaxis and motility genes were expressed at similar levels in LB and BHI, but at low to undetectable levels in vitreous, although motility is an important phenotype for B. cereus in the eye. Superoxide dismutase, a potential inhibitor of neutrophil activity in the eye during infection, was the most highly expressed gene in vitreous. Genes previously reported to be important to intraocular virulence were expressed at low levels in vitreous under these conditions, possibly because in vivo cues are required for higher level expression. Genes expressed in vitreous may contribute to the unique virulence of B. cereus endophthalmitis, and future analysis of the B. cereus virulome in the eye will identify those expressed in vivo, which could potentially be targeted to arrest virulence.

ACS Style

Phillip S. Coburn; Frederick C. Miller; Morgan A. Enty; Craig Land; Austin L. LaGrow; Huzzatul Mursalin; Michelle C. Callegan. Expression of Bacillus cereus Virulence-Related Genes in an Ocular Infection-Related Environment. Microorganisms 2020, 8, 607 .

AMA Style

Phillip S. Coburn, Frederick C. Miller, Morgan A. Enty, Craig Land, Austin L. LaGrow, Huzzatul Mursalin, Michelle C. Callegan. Expression of Bacillus cereus Virulence-Related Genes in an Ocular Infection-Related Environment. Microorganisms. 2020; 8 (4):607.

Chicago/Turabian Style

Phillip S. Coburn; Frederick C. Miller; Morgan A. Enty; Craig Land; Austin L. LaGrow; Huzzatul Mursalin; Michelle C. Callegan. 2020. "Expression of Bacillus cereus Virulence-Related Genes in an Ocular Infection-Related Environment." Microorganisms 8, no. 4: 607.

Preprint content
Published: 18 March 2020
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Bacillus cereus produces many factors linked to pathogenesis and is recognized for causing gastrointestinal toxemia and infections. B. cereus also causes a fulminant and often blinding intraocular infection called endophthalmitis. We reported that the PlcR/PapR system regulates intraocular virulence, but the specific factors that contribute to B. cereus virulence in the eye remain elusive. Here, we compared gene expression in ex vivo vitreous humor with expression in Luria Bertani (LB) and Brain Heart Infusion (BHI) broth by RNA-Seq. The expression of several cytolytic toxins in vitreous was less than or similar to levels observed in BHI or LB. Regulators of virulence genes, including PlcR/PapR, were expressed in vitreous. PlcR/PapR was expressed at low levels, though we had reported that PlcR-deficient B. cereus was attenuated in the eye. Chemotaxis and motility genes were expressed at similar levels in LB and BHI, but at low to undetectable levels in vitreous, although motility is an important phenotype for B. cereus in the eye. Superoxide dismutase, a potential inhibitor of neutrophil activity in the eye during infection, was the most highly expressed gene in vitreous. Genes previously reported to be important to intraocular virulence were expressed at low levels in vitreous under these conditions, possibly because in vivo cues are required for higher level expression. Genes expressed in vitreous may contribute to the unique virulence of B. cereus endophthalmitis, and future analysis of the B. cereus virulome in the eye will identify those expressed in vivo, which could potentially be targeted to arrest virulence.Impact statementB. cereus is the causative agent of gastrointestinal infections, but can also cause a serious infection of the eye that often results in blindness or enucleation. Current therapeutic measures often fail to mitigate these poor outcomes. This necessitates the development of new treatment modalities based on new targets. To begin to better define those B. cereus factors with roles in intraocular infection, we analyzed the expression of genes related to gastrointestinal infections, as well as those with both known and hypothesized roles in intraocular infections, after growth in an ex vivo vitreous. Potentially targetable candidate genes were demonstrated to be expressed in vitreous, which suggests that these genes might contribute to the unique virulence of B. cereus endophthalmitis. Importantly, our results lay the groundwork for assessing the expression of these genes in vivo and defining the virulome of B. cereus in intraocular infections.

ACS Style

Phillip S. Coburn; Frederick C. Miller; Morgan A. Enty; Craig Land; Austin L. LaGrow; Huzzatul Mursalin; Michelle C. Callegan. Expression of Bacillus cereus Virulence-Related Genes in an Ocular Infection-Related Environment. 2020, 1 .

AMA Style

Phillip S. Coburn, Frederick C. Miller, Morgan A. Enty, Craig Land, Austin L. LaGrow, Huzzatul Mursalin, Michelle C. Callegan. Expression of Bacillus cereus Virulence-Related Genes in an Ocular Infection-Related Environment. . 2020; ():1.

Chicago/Turabian Style

Phillip S. Coburn; Frederick C. Miller; Morgan A. Enty; Craig Land; Austin L. LaGrow; Huzzatul Mursalin; Michelle C. Callegan. 2020. "Expression of Bacillus cereus Virulence-Related Genes in an Ocular Infection-Related Environment." , no. : 1.

Original research article
Published: 12 February 2020 in Frontiers in Immunology
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Bacillus endophthalmitis is a severe intraocular infection. Hallmarks of Bacillus endophthalmitis include robust inflammation and rapid loss of vision. We reported that the absence of Bacillus surface layer protein (SLP) significantly blunted endophthalmitis severity. Here, we further investigated SLP in the context of Bacillus-retinal cell interactions and innate immune pathways to explore the mechanisms by which SLP contributes to intraocular inflammation. We compared phenotypes of Wild-type (WT) and SLP deficient (ΔslpA) Bacillus thuringiensis by analyzing bacterial adherence to and phagocytosis by human retinal Muller cells and phagocytosis by mouse neutrophils. Innate immune receptor activation by the Bacillus envelope and purified SLP was analyzed using TLR2/4 reporter cell lines. A synthetic TLR2/4 inhibitor was used as a control for this receptor activation. To induce endophthalmitis, mouse eyes were injected intravitreally with 100 CFU WT or ΔslpA B. thuringiensis. A group of WT infected mice was treated intravitreally with a TLR2/4 inhibitor at 4 h postinfection. At 10 h postinfection, infected eyes were analyzed for viable bacteria, inflammation, and retinal function. We observed that B. thuringiensis SLPs contributed to retinal Muller cell adherence, and protected this pathogen from Muller cell- and neutrophil-mediated phagocytosis. We found that B. thuringiensis envelope activated TLR2 and, surprisingly, TLR4, suggesting the presence of a surface-associated TLR4 agonist in Bacillus. Further investigation showed that purified SLP from B. thuringiensis activated TLR4, as well as TLR2 in vitro. Growth of WT B. thuringiensis was significantly higher and caused greater inflammation in untreated eyes than in eyes treated with the TLR2/4 inhibitor. Retinal function analysis also showed greater retention of A-wave and B-wave function in infected eyes treated with the TLR2/4 inhibitor. The TLR2/4 inhibitor was not antibacterial in vitro, and did not cause inflammation when injected into uninfected eyes. Taken together, these results suggest a potential role for Bacillus SLP in host-bacterial interactions, as well as in endophthalmitis pathogenesis via TLR2- and TLR4-mediated pathways.

ACS Style

Huzzatul Mursalin; Phillip S. Coburn; Erin Livingston; Frederick C. Miller; Roger Astley; Ana L. Flores-Mireles; Michelle C. Callegan. Bacillus S-Layer-Mediated Innate Interactions During Endophthalmitis. Frontiers in Immunology 2020, 11, 215 .

AMA Style

Huzzatul Mursalin, Phillip S. Coburn, Erin Livingston, Frederick C. Miller, Roger Astley, Ana L. Flores-Mireles, Michelle C. Callegan. Bacillus S-Layer-Mediated Innate Interactions During Endophthalmitis. Frontiers in Immunology. 2020; 11 ():215.

Chicago/Turabian Style

Huzzatul Mursalin; Phillip S. Coburn; Erin Livingston; Frederick C. Miller; Roger Astley; Ana L. Flores-Mireles; Michelle C. Callegan. 2020. "Bacillus S-Layer-Mediated Innate Interactions During Endophthalmitis." Frontiers in Immunology 11, no. : 215.

Review article
Published: 04 February 2020 in Experimental Eye Research
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Bacillus cereus (B. cereus) endophthalmitis is a devastating intraocular infection primarily associated with post-traumatic injuries. The majority of these infections result in substantial vision loss, if not loss of the eye itself, within 12–48 h. Multifactorial mechanisms that lead to the innate intraocular inflammatory response during this disease include the combination of robust bacterial replication, migration of the organism throughout the eye, and toxin production by the organism. Therefore, the window of therapeutic intervention in B. cereus endophthalmitis is quite narrow compared to that of other pathogens which cause this disease. Understanding the interaction of bacterial and host factors is critical in understanding the disease and formulating more rational therapeutics for salvaging vision. In this review, we will discuss clinical and research findings related to B. cereus endophthalmitis in terms of the organism's virulence and inflammogenic potential, and strategies for improving of current therapeutic regimens for this blinding disease.

ACS Style

Huzzatul Mursalin; Erin T. Livingston; Michelle C. Callegan. The cereus matter of Bacillus endophthalmitis. Experimental Eye Research 2020, 193, 107959 -107959.

AMA Style

Huzzatul Mursalin, Erin T. Livingston, Michelle C. Callegan. The cereus matter of Bacillus endophthalmitis. Experimental Eye Research. 2020; 193 ():107959-107959.

Chicago/Turabian Style

Huzzatul Mursalin; Erin T. Livingston; Michelle C. Callegan. 2020. "The cereus matter of Bacillus endophthalmitis." Experimental Eye Research 193, no. : 107959-107959.

Review
Published: 07 November 2019 in Microorganisms
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Some tissues of the eye are susceptible to damage due to their exposure to the outside environment and inability to regenerate. Immune privilege, although beneficial to the eye in terms of homeostasis and protection, can be harmful when breached or when an aberrant response occurs in the face of challenge. In this review, we highlight the role of the PMN (polymorphonuclear leukocyte) in different bacterial ocular infections that invade the immune privileged eye at the anterior and posterior segments: keratitis, conjunctivitis, uveitis, and endophthalmitis. Interestingly, the PMN response from the host seems to be necessary for pathogen clearance in ocular disease, but the inflammatory response can also be detrimental to vision retention. This “Pyrrhic Victory” scenario is explored in each type of ocular infection, with details on PMN recruitment and response at the site of ocular infection. In addition, we emphasize the differences in PMN responses between each ocular disease and its most common corresponding bacterial pathogen. The in vitro and animal models used to identify PMN responses, such as recruitment, phagocytosis, degranulation, and NETosis, are also outlined in each ocular infection. This detailed study of the ocular acute immune response to infection could provide novel therapeutic strategies for blinding diseases, provide more general information on ocular PMN responses, and reveal areas of bacterial ocular infection research that lack PMN response studies.

ACS Style

Erin T. Livingston; Huzzatul Mursalin; Michelle C. Callegan. A Pyrrhic Victory: The PMN Response to Ocular Bacterial Infections. Microorganisms 2019, 7, 537 .

AMA Style

Erin T. Livingston, Huzzatul Mursalin, Michelle C. Callegan. A Pyrrhic Victory: The PMN Response to Ocular Bacterial Infections. Microorganisms. 2019; 7 (11):537.

Chicago/Turabian Style

Erin T. Livingston; Huzzatul Mursalin; Michelle C. Callegan. 2019. "A Pyrrhic Victory: The PMN Response to Ocular Bacterial Infections." Microorganisms 7, no. 11: 537.

Immunology and microbiology
Published: 03 September 2019 in Investigative Opthalmology & Visual Science
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Purpose: Bacillus causes a sight-threating infection of the posterior segment of the eye. The robust intraocular inflammatory response in this disease is likely activated via host innate receptor interactions with components of the Bacillus cell envelope. S-layer proteins (SLPs) of some Gram-positive pathogens contribute to the pathogenesis of certain infections. The potential contributions of SLPs in eye infection pathogenesis have not been considered. Here, we explored the role of a Bacillus SLP (SlpA) in endophthalmitis pathogenesis. Methods: The phenotypes and infectivity of wild-type (WT) and S-layer deficient (ΔslpA) Bacillus thuringiensis were compared. Experimental endophthalmitis was induced in C57BL/6J mice by intravitreally injecting 100-CFU WT or ΔslpA B. thuringiensis. Infected eyes were analyzed by bacterial counts, retinal function analysis, histology, and inflammatory cell influx. SLP-induced inflammation was also analyzed in vitro. Muller cells (MIO-M1) were treated with purified SLP. Nuclear factor-κB (NF-κB) DNA binding was measured by ELISA and expression of proinflammatory mediators from Muller cells was measured by RT-qPCR. Results: Tested phenotypes of WT and ΔslpA B. thuringiensis were similar, with the exception of absence of the S-layer in the ΔslpA mutant. Intraocular growth of WT and ΔslpA B. thuringiensis was also similar. However, eyes infected with the ΔslpA mutant had significantly reduced inflammatory cell influx, less inflammatory damage to the eyes, and significant retention of retinal function compared with WT-infected eyes. SLP was also a potent stimulator of the NF-κB pathway and induced the expression of proinflammatory mediators (IL6, TNFα, CCL2, and CXCL-1) in human retinal Muller cells. Conclusions: Taken together, our results suggest that SlpA contributes to the pathogenesis of Bacillus endophthalmitis, potentially by triggering innate inflammatory pathways in the retina.

ACS Style

Huzzatul Mursalin; Phillip S. Coburn; Erin Livingston; Frederick C. Miller; Roger Astley; Agnès Fouet; Michelle C. Callegan. S-layer Impacts the Virulence ofBacillusin Endophthalmitis. Investigative Opthalmology & Visual Science 2019, 60, 3727 -3739.

AMA Style

Huzzatul Mursalin, Phillip S. Coburn, Erin Livingston, Frederick C. Miller, Roger Astley, Agnès Fouet, Michelle C. Callegan. S-layer Impacts the Virulence ofBacillusin Endophthalmitis. Investigative Opthalmology & Visual Science. 2019; 60 (12):3727-3739.

Chicago/Turabian Style

Huzzatul Mursalin; Phillip S. Coburn; Erin Livingston; Frederick C. Miller; Roger Astley; Agnès Fouet; Michelle C. Callegan. 2019. "S-layer Impacts the Virulence ofBacillusin Endophthalmitis." Investigative Opthalmology & Visual Science 60, no. 12: 3727-3739.

Journal article
Published: 26 June 2019 in mSphere
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Endophthalmitis is a blinding consequence of bacterial invasion of the interior of the eye. Because of increases in the numbers of ocular surgeries and intraocular injections, the incidence of endophthalmitis is steadily increasing. Staphylococcus aureus , Enterococcus faecalis , Streptococcus pneumoniae , and Bacillus cereus are leading causes of infection following ocular procedures and trauma and are increasingly more difficult to treat due to multidrug resistance. Each of these pathogens produces pore-forming toxins that contribute to the pathogenesis of endophthalmitis. Treatment of these infections with antibiotics alone is insufficient to prevent damage to the retina and vision loss. Therefore, novel therapeutics are needed that include agents that neutralize bacterial pore-forming toxins. Here, we demonstrate that biomimetic nanosponges neutralize pore-forming toxins from these ocular pathogens and aid in preserving retinal function. Nanosponges may represent a new form of adjunct antitoxin therapy for serious potentially blinding intraocular infections.

ACS Style

Phillip S. Coburn; Frederick C. Miller; Austin L. LaGrow; Craig Land; Huzzatul Mursalin; Erin Livingston; Omar Amayem; Yijie Chen; Weiwei Gao; Liangfang Zhang; Michelle C. Callegan. Disarming Pore-Forming Toxins with Biomimetic Nanosponges in Intraocular Infections. mSphere 2019, 4, e00262-19 .

AMA Style

Phillip S. Coburn, Frederick C. Miller, Austin L. LaGrow, Craig Land, Huzzatul Mursalin, Erin Livingston, Omar Amayem, Yijie Chen, Weiwei Gao, Liangfang Zhang, Michelle C. Callegan. Disarming Pore-Forming Toxins with Biomimetic Nanosponges in Intraocular Infections. mSphere. 2019; 4 (3):e00262-19.

Chicago/Turabian Style

Phillip S. Coburn; Frederick C. Miller; Austin L. LaGrow; Craig Land; Huzzatul Mursalin; Erin Livingston; Omar Amayem; Yijie Chen; Weiwei Gao; Liangfang Zhang; Michelle C. Callegan. 2019. "Disarming Pore-Forming Toxins with Biomimetic Nanosponges in Intraocular Infections." mSphere 4, no. 3: e00262-19.

Review
Published: 19 June 2019 in Toxins
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Staphylococcus aureus (S. aureus) is a common pathogen of the eye, capable of infecting external tissues such as the tear duct, conjunctiva, and the cornea, as well the inner and more delicate anterior and posterior chambers. S. aureus produces numerous toxins and enzymes capable of causing profound damage to tissues and organs, as well as modulating the immune response to these infections. Unfortunately, in the context of ocular infections, this can mean blindness for the patient. The role of α-toxin in corneal infection (keratitis) and infection of the interior of the eye (endophthalmitis) has been well established by comparing virulence in animal models and α-toxin-deficient isogenic mutants with their wild-type parental strains. The importance of other toxins, such as β-toxin, γ-toxin, and Panton–Valentine leukocidin (PVL), have been analyzed to a lesser degree and their roles in eye infections are less clear. Other toxins such as the phenol-soluble modulins have yet to be examined in any animal models for their contributions to virulence in eye infections. This review discusses the state of current knowledge of the roles of S. aureus toxins in eye infections and the controversies existing as a result of the use of different infection models. The strengths and limitations of these ocular infection models are discussed, as well as the need for physiological relevance in the study of staphylococcal toxins in these models.

ACS Style

Roger Astley; Frederick C. Miller; Huzzatul Mursalin; Phillip S. Coburn; Michelle C. Callegan. An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation. Toxins 2019, 11, 356 .

AMA Style

Roger Astley, Frederick C. Miller, Huzzatul Mursalin, Phillip S. Coburn, Michelle C. Callegan. An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation. Toxins. 2019; 11 (6):356.

Chicago/Turabian Style

Roger Astley; Frederick C. Miller; Huzzatul Mursalin; Phillip S. Coburn; Michelle C. Callegan. 2019. "An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation." Toxins 11, no. 6: 356.

Review article
Published: 28 May 2019 in Progress in Retinal and Eye Research
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Bacterial infection of the posterior segment of the eye (endophthalmitis) leads to a robust host response that often results in irreversible damage to the layers of the retina, significant vision loss, and in some patients, enucleation of the globe. While a great deal of effort has gone into understanding the role of bacterial virulence factors in disease initiation and propagation, it is becoming increasingly clear that the host response to infection plays a major role in causing the damage associated with endophthalmitis. Researchers have identified the host receptors which detect infecting organisms and initiate the cascade of events that result in inflammation. This inflammation may damage nonregenerative tissues of the eye while attempting to clear the infection. Both Gram-positive and Gram-negative bacteria can cause endophthalmitis. These organisms initiate an immune response by activating toll-like receptor (TLR) pathways. Once an inflammatory response is initiated, the expression of immunomodulators, such as proinflammatory chemokines and cytokines, affect the recruitment of PMNs and other inflammatory cells into the eye. We and others have reported that knockout mice that do not express specific inflammatory pathways and molecules have an attenuated response to infection and retain significant retinal function. These findings suggest that host immune mediators are important components of the response to infections in the posterior segment of the eye, and the timing and level of their production may be related to the severity of the damage and the ultimate visual outcome. If that is the case, a better understanding of the complex and often redundant role of these pathways and inflammatory mediators may identify host molecules as potential anti-inflammatory therapeutic targets. This review highlights potential anti-inflammatory targets during acute inflammation in endophthalmitis, compares and contrasts those with findings in other models of ocular inflammation, and translates current immunomodulatory strategies for other types of infection and inflammation to this blinding disease. Given the poor visual outcomes seen in patients treated with antibiotics alone or in combination with corticosteroids, immunomodulation in addition to antibiotic therapy might be more effective in preserving vision than current regimens.

ACS Style

Frederick C. Miller; Phillip S. Coburn; Mursalin Md Huzzatul; Austin L. LaGrow; Erin Livingston; Michelle C. Callegan. Targets of immunomodulation in bacterial endophthalmitis. Progress in Retinal and Eye Research 2019, 73, 100763 -100763.

AMA Style

Frederick C. Miller, Phillip S. Coburn, Mursalin Md Huzzatul, Austin L. LaGrow, Erin Livingston, Michelle C. Callegan. Targets of immunomodulation in bacterial endophthalmitis. Progress in Retinal and Eye Research. 2019; 73 ():100763-100763.

Chicago/Turabian Style

Frederick C. Miller; Phillip S. Coburn; Mursalin Md Huzzatul; Austin L. LaGrow; Erin Livingston; Michelle C. Callegan. 2019. "Targets of immunomodulation in bacterial endophthalmitis." Progress in Retinal and Eye Research 73, no. : 100763-100763.

Journal article
Published: 27 December 2017 in mSphere
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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.

ACS Style

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 Enterococcus faecalis Cytolysin. mSphere 2017, 2, e00335-17 .

AMA Style

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 Enterococcus faecalis Cytolysin. mSphere. 2017; 2 (6):e00335-17.

Chicago/Turabian Style

Austin L. LaGrow; Phillip S. Coburn; Frederick C. Miller; Craig Land; Salai Madhumathi Parkunan; Brian T. Luk; Weiwei Gao; Liangfang Zhang; Michelle C. Callegan. 2017. "A Novel Biomimetic Nanosponge Protects the Retina from the Enterococcus faecalis Cytolysin." mSphere 2, no. 6: e00335-17.

Journal article
Published: 20 March 2017 in Experimental Eye Research
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Bacterial endophthalmitis is a potentially blinding intraocular infection. The bacterium Bacillus cereus causes a devastating form of this disease which progresses rapidly, resulting in significant inflammation and loss of vision within a few days. The outer surface of B. cereus incites the intraocular inflammatory response, likely through interactions with innate immune receptors such as TLRs. This study analyzed the role of B. cereus pili, adhesion appendages located on the bacterial surface, in experimental endophthalmitis. To test the hypothesis that the presence of pili contributed to intraocular inflammation and virulence, we analyzed the progress of experimental endophthalmitis in mouse eyes infected with wild type B. cereus (ATCC 14579) or its isogenic pilus-deficient mutant (ΔbcpA-srtD-bcpB or ΔPil). One hundred CFU were injected into the mid-vitreous of one eye of each mouse. Infections were analyzed by quantifying intraocular bacilli and retinal function loss, and by histology from 0 to 12 h postinfection. In vitro growth and hemolytic phenotypes of the infecting strains were also compared. There was no difference in hemolytic activity (1:8 titer), motility, or in vitro growth (p > 0.05, every 2 h, 0–18 h) between wild type B. cereus and the ΔPil mutant. However, infected eyes contained greater numbers of wild type B. cereus than ΔPil during the infection course (p ≤ 0.05, 3–12 h). Eyes infected with wild type B. cereus experienced greater losses in retinal function than eyes infected with the ΔPil mutant, but the differences were not always significant. Eyes infected with ΔPil or wild type B. cereus achieved similar degrees of severe inflammation. The results indicated that the intraocular growth of pilus-deficient B. cereus may have been better controlled, leading to a trend of greater retinal function in eyes infected with the pilus-deficient strain. Although this difference was not enough to significantly alter the severity of the inflammatory response, these results suggest a potential role for pili in protecting B. cereus from clearance during the early stages of endophthalmitis, which is a newly described virulence mechanism for this organism and this infection.

ACS Style

Michelle C. Callegan; Salai Madhumathi Parkunan; C. Blake Randall; Phillip S. Coburn; Frederick C. Miller; Austin L. LaGrow; Roger A. Astley; Craig Land; So-Young Oh; Olaf Schneewind. The role of pili in Bacillus cereus intraocular infection. Experimental Eye Research 2017, 159, 69 -76.

AMA Style

Michelle C. Callegan, Salai Madhumathi Parkunan, C. Blake Randall, Phillip S. Coburn, Frederick C. Miller, Austin L. LaGrow, Roger A. Astley, Craig Land, So-Young Oh, Olaf Schneewind. The role of pili in Bacillus cereus intraocular infection. Experimental Eye Research. 2017; 159 ():69-76.

Chicago/Turabian Style

Michelle C. Callegan; Salai Madhumathi Parkunan; C. Blake Randall; Phillip S. Coburn; Frederick C. Miller; Austin L. LaGrow; Roger A. Astley; Craig Land; So-Young Oh; Olaf Schneewind. 2017. "The role of pili in Bacillus cereus intraocular infection." Experimental Eye Research 159, no. : 69-76.

Journal article
Published: 10 June 2016 in Journal of Leukocyte Biology
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During intraocular bacterial infections, the primary innate responders are neutrophils, which may cause bystander damage to the retina or perturb the clarity of the visual axis. We hypothesized that cytokine IL-6 and chemokine CXCL1 contributed to rapid neutrophil recruitment during Bacillus cereus endophthalmitis, a severe form of intraocular infection that is characterized by explosive inflammation and retinal damage that often leads to rapid vision loss. To test this hypothesis, we compared endophthalmitis pathogenesis in C57BL/6J, IL-6-/-, and CXCL1-/- mice. Bacterial growth in eyes of CXCL1-/-, IL-6-/-, and C67BL/6J mice was similar. Retinal function retention was greater in eyes of IL-6-/- and CXCL1-/- mice compared with that of C57BL/6J, despite these eyes having similar bacterial burdens. Neutrophil influx into eyes of CXCL1-/- mice was reduced to a greater degree compared with that of eyes of IL6-/- mice. Histology confirmed significantly less inflammation in eyes of CXCL1-/- mice, but similar degrees of inflammation in IL6-/- and C57BL/6J eyes. Because inflammation was reduced in eyes of infected CXCL1-/- mice, we tested the efficacy of anti-CXCL1 in B. cereus endophthalmitis. Retinal function was retained to a greater degree and there was less overall inflammation in eyes treated with anti-CXCL1, which suggested that anti-CXCL1 may have therapeutic efficacy in limiting inflammation during B. cereus endophthalmitis. Taken together, our results indicate that absence of IL-6 did not affect overall pathogenesis of endophthalmitis. In contrast, absence of CXCL1, in CXCL1-/- mice or after anti-CXCL1 treatment, led to an improved clinical outcome. Our findings suggest a potential benefit in targeting CXCL1 to control inflammation during B. cereus and perhaps other types of intraocular infections.

ACS Style

Salai Madhumathi Parkunan; C. Blake Randall; Roger A. Astley; Glaucia C. Furtado; Sergio A. Lira; Michelle C. Callegan. CXCL1, but not IL-6, significantly impacts intraocular inflammation during infection. Journal of Leukocyte Biology 2016, 100, 1125 -1134.

AMA Style

Salai Madhumathi Parkunan, C. Blake Randall, Roger A. Astley, Glaucia C. Furtado, Sergio A. Lira, Michelle C. Callegan. CXCL1, but not IL-6, significantly impacts intraocular inflammation during infection. Journal of Leukocyte Biology. 2016; 100 (5):1125-1134.

Chicago/Turabian Style

Salai Madhumathi Parkunan; C. Blake Randall; Roger A. Astley; Glaucia C. Furtado; Sergio A. Lira; Michelle C. Callegan. 2016. "CXCL1, but not IL-6, significantly impacts intraocular inflammation during infection." Journal of Leukocyte Biology 100, no. 5: 1125-1134.

Research article
Published: 19 May 2016 in PLOS ONE
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The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is not required for the development of EBE, but toxin production may facilitate EBE pathogenesis.

ACS Style

Phillip S. Coburn; Brandt J. Wiskur; Frederick C. Miller; Austin L. LaGrow; Roger Astley; Michael H. Elliott; Michelle C. Callegan. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction. PLOS ONE 2016, 11, e0154560 -e0154560.

AMA Style

Phillip S. Coburn, Brandt J. Wiskur, Frederick C. Miller, Austin L. LaGrow, Roger Astley, Michael H. Elliott, Michelle C. Callegan. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction. PLOS ONE. 2016; 11 (5):e0154560-e0154560.

Chicago/Turabian Style

Phillip S. Coburn; Brandt J. Wiskur; Frederick C. Miller; Austin L. LaGrow; Roger Astley; Michael H. Elliott; Michelle C. Callegan. 2016. "Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction." PLOS ONE 11, no. 5: e0154560-e0154560.

Review article
Published: 03 May 2016 in Progress in Retinal and Eye Research
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Bacterial endophthalmitis is an infection and inflammation of the posterior segment of the eye which can result in significant loss of visual acuity. Even with prompt antibiotic, anti-inflammatory and surgical intervention, vision and even the eye itself may be lost. For the past century, experimental animal models have been used to examine various aspects of the pathogenesis and pathophysiology of bacterial endophthalmitis, to further the development of anti-inflammatory treatment strategies, and to evaluate the pharmacokinetics and efficacies of antibiotics. Experimental models allow independent control of many parameters of infection and facilitate systematic examination of infection outcomes. While no single animal model perfectly reproduces the human pathology of bacterial endophthalmitis, investigators have successfully used these models to understand the infectious process and the host response, and have provided new information regarding therapeutic options for the treatment of bacterial endophthalmitis. This review highlights experimental animal models of endophthalmitis and correlates this information with the clinical setting. The goal is to identify knowledge gaps that may be addressed in future experimental and clinical studies focused on improvements in the therapeutic preservation of vision during and after this disease.

ACS Style

Roger Astley; Phillip S. Coburn; Salai Madhumathi Parkunan; Michelle C. Callegan. Modeling intraocular bacterial infections. Progress in Retinal and Eye Research 2016, 54, 30 -48.

AMA Style

Roger Astley, Phillip S. Coburn, Salai Madhumathi Parkunan, Michelle C. Callegan. Modeling intraocular bacterial infections. Progress in Retinal and Eye Research. 2016; 54 ():30-48.

Chicago/Turabian Style

Roger Astley; Phillip S. Coburn; Salai Madhumathi Parkunan; Michelle C. Callegan. 2016. "Modeling intraocular bacterial infections." Progress in Retinal and Eye Research 54, no. : 30-48.