title: Role of Staphylococcus aureus Virulence Factors in Inducing Inflammation and Vascular Permeability in a Mouse Model of Bacterial Endophthalmitis.
abstract: Staphylococcus (S.) aureus is a common causative agent of bacterial endophthalmitis, a vision threatening complication of eye surgeries. The relative contribution of S. aureus virulence factors in the pathogenesis of endophthalmitis remains unclear. Here, we comprehensively analyzed the development of intraocular inflammation, vascular permeability, and the loss of retinal function in C57BL/6 mouse eyes, challenged with live S. aureus, heat-killed S. aureus (HKSA), peptidoglycan (PGN), lipoteichoic acid (LTA), staphylococcal protein A (SPA), α-toxin, and Toxic-shock syndrome toxin 1 (TSST1). Our data showed a dose-dependent (range 0.01 μg/eye to 1.0 μg/eye) increase in the levels of inflammatory mediators by all virulence factors. The cell wall components, particularly PGN and LTA, seem to induce higher levels of TNF-α, IL-6, KC, and MIP2, whereas the toxins induced IL-1β. Similarly, among the virulence factors, PGN induced higher PMN infiltration. The vascular permeability assay revealed significant leakage in eyes challenged with live SA (12-fold) and HKSA (7.3-fold), in comparison to other virulence factors (~2-fold) and controls. These changes coincided with retinal tissue damage, as evidenced by histological analysis. The electroretinogram (ERG) analysis revealed a significant decline in retinal function in eyes inoculated with live SA, followed by HKSA, SPA, and α-toxin. Together, these findings demonstrate the differential innate responses of the retina to S. aureus virulence factors, which contribute to intraocular inflammation and retinal function loss in endophthalmitis.
authors.affiliation: Department of Ophthalmology, Kresge Eye Institute, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Ophthalmology, Kresge Eye Institute, Wayne State University, Detroit, Michigan, United States of America; Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan, United States of America; Department of Immunology and Microbiology, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D009877:Endophthalmitis / Q000150:complications / Q000382:microbiology* / Q000503:physiopathology; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005654:Fundus Oculi; D007249:Inflammation / Q000150:complications / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D010457:Peptidoglycan / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013203:Staphylococcal Infections / Q000150:complications / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D010457:Peptidoglycan; D037521:Virulence Factors