Role of Staphylococcus aureus Virulence Factors in Inducing Inflammation and Vascular Permeability in a Mouse Model of Bacterial Endophthalmitis.

Ajay Kumar,Ashok Kumar,Lbachir BenMohamed

doi:10.1371/journal.pone.0128423

Ajay Kumar, Ashok Kumar + Show 1 more

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https://doi.org/10.1371/journal.pone.0128423

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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.

Highlights

Infectious endophthalmitis is one of the most devastating complications of ophthalmic surgeries and penetrating injuries [1]
S. aureus Virulence Factors and Endophthalmitis infectious endophthalmitis varies widely depending upon the organism involved, ranging from therapeutically responsive infections to therapeutically challenging infections caused by more virulent pathogens such as Bacillus cereus [3, 4] and Staphylococcus(S) aureus [5,6,7]
To investigate the role of S. aureus virulence factors in generating inflammatory responses, the eyes of C57BL/6 mice were injected with various doses of S. aureus cell wall components and toxins for 24h

Summary

Introduction

Infectious endophthalmitis is one of the most devastating complications of ophthalmic surgeries and penetrating injuries [1]. The most common isolated microorganisms are Grampositive staphylococci, which constitute up to 90% of all bacterial pathogens [2]. S. aureus Virulence Factors and Endophthalmitis infectious endophthalmitis varies widely depending upon the organism involved, ranging from therapeutically responsive infections to therapeutically challenging infections caused by more virulent pathogens such as Bacillus cereus [3, 4] and Staphylococcus(S) aureus [5,6,7]. As one of the most feared ocular pathogens, S. aureus causes severe intraocular inflammation, significant vision loss, and can even cause loss of the eye [8, 9]. Despite therapeutic and surgical interventions, endophthalmitis results in partial or complete visual loss within a few days of microbial inoculation [10]

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