S-layer Impacts the Virulence ofBacillusin Endophthalmitis
| Autor: | Agnès Fouet, Michelle C. Callegan, Erin Livingston, Roger A. Astley, Frederick C. Miller, Huzzatul Mursalin, Phillip S. Coburn |
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| Přispěvatelé: | Department of Microbiology and Immunology [Oklahoma City, OK, USA], University of Oklahoma Health Sciences Center (OUHSC), Department of Ophthalmology [Oklahoma City, OK, USA], Dean McGee Eye Institute [Oklahoma City, OK, USA], Department of Cell Biology and Department of Family and Preventive Medicine [Oklahoma City, OK, USA], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Oklahoma Center for Neuroscience [Oklahoma City, OK, USA], Supported by National Institutes of Health grants R01EY028810 and R01EY024140 (to MCC). Our research is also supported in part by National Institutes of Health grants R01EY025947 and R21EY028066 (to MCC), National Eye Institutes Vision Core Grant P30EY027125 (to MCC), a Presbyterian Health Foundation Research Support Grant Award (to MCC), a Presbyterian Health Foundation Equipment Grant (to Robert E. Anderson, OUHSC), and an unrestricted grant to the Dean A. McGee Eye Institute from Research to Prevent Blindness. |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
retina genetic structures Colony Count Microbial Bacillus Eye Infections Bacterial Pathogenesis Mice Endophthalmitis [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Bacillus thuringiensis bacteria Immunology and Microbiology Membrane Glycoproteins Virulence medicine.diagnostic_test NF-kappa B 3. Good health endophthalmitis Models Animal Cytokines Tumor necrosis factor alpha medicine.symptom blindness Ependymoglial Cells 030106 microbiology Enzyme-Linked Immunosorbent Assay Inflammation Biology Real-Time Polymerase Chain Reaction Proinflammatory cytokine Microbiology 03 medical and health sciences Bacterial Proteins Microscopy Electron Transmission Electroretinography medicine Animals [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs Gram-Positive Bacterial Infections Eye infection medicine.disease biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology eye diseases Mice Inbred C57BL 030104 developmental biology inflammation sense organs |
| Zdroj: | Investigative Ophthalmology & Visual Science Investigative Ophthalmology & Visual Science, Association for Research in Vision and Ophthalmology, 2019, 60 (12), pp.3727-3739. ⟨10.1167/iovs.19-27453⟩ |
| ISSN: | 1552-5783 0146-0404 |
| DOI: | 10.1167/iovs.19-27453 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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