An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation

Abstract

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.

Keywords: Staphylococcus aureus; enzymes; eye; in vivo models; infection; toxins.

Figure 1

Phenotypes of Staphylococcus aureus (S. aureus). (A) Gram stain of S. aureus. Magnification, 100×. (B) S. aureus grown on 5% sheep blood agar overnight at 37 °C. Note the characteristic zones of β-hemolysis surrounding each colony. (C) S. aureus grown on mannitol salt agar overnight at 37 °C. S. aureus, unlike other staphylococci, ferments mannitol, resulting in acid production and the classic yellow halo within the deep pink agar.

Figure 2

S. aureus virulence factors contribute to the pathogenesis of ocular infections. (A) S. aureus contains numerous virulence factors in its armamentarium which assists in antibiotic resistance, adherence to tissue, interactions with innate immunity, and spread of infection. (B) S. aureus toxins which have been analyzed in experimental infection models include α-toxin, β-toxin, γ-toxin, and Panton–Valentine leukocidin (PVL). The contribution of these toxins to ocular infections is strain-and model-dependent, as discussed below.

Figure 3

S. aureus-induced corneal ulcers in humans and rabbits. (A) A corneal ulcer with superficial stromal infiltration and anterior chamber hypopyon in a human eye infected with MRSA. Copyright © Lee et al., 2010 [82]. (B) S. aureus keratitis in a rabbit eye. Black arrow indicates inflammatory cell infiltration and staphylococcal microcolonies formed in the corneal stroma. White arrow indicates the edge of the epithelial erosion stained with fluorescein. Copyright © Marquart et al., 2011 [83]. These are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.