Staphylococcus aureus alpha-hemolysin impairs corneal epithelial wound healing and promotes intracellular bacterial invasion. (April 2019)

• Record Type: Journal Article
• Authors: Putra, Ilham; Rabiee, Behnam; Anwar, Khandaker N.; Gidfar, Sanaz; Shen, Xiang; Babalooee, Mehrdad; Ghassemi, Mahmood; Afsharkhamseh, Neda; Bakhsh, Saaquib; Missiakas, Dominique; Nezamabadi, Ali; Milani, Behrad; Eslani, Medi; Djalilian, Ali R.
• Is Part Of: Experimental eye research. Volume 181(2019)
• Page Start: 263
• Page End: 270
• Publication Date: 2019-04
• Subjects: Staphylococcus aureus -- Alpha-toxin -- Alpha-hemolysin -- Cornea -- Keratitis -- Infection -- Wound healing; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2019.02.019
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Colonization by Staphylococcus aureus (S. aureus) has been implicated in many infectious and wound healing disorders. This study was performed to characterize the pathogenic role of S. aureus alpha-hemolysin (alpha-toxin) in corneal epithelial wound healing and infectious keratitis in the setting of a corneal wound. The effect of wild-type and isogenic Hla mutant (α-hemolysin gene deleted) S. aureus bacteria and conditioned media on corneal epithelial wound healing was tested in vitro using a scratch assay and in vivo using a murine epithelial debridement model. The invasiveness of wild-type and Hla mutant S. aureus was evaluated in vitro in human corneal epithelial cells and in vivo in a murine model of infectious keratitis following total epithelial debridement. S. aureus and its conditioned media significantly delayed epithelial wound closure both in vitro (P < 0.05) and in vivo (P < 0.05) . The effect of S. aureus on wound healing was significantly diminished with the Hla mutant strain (P < 0.05). Likewise, compared to the wild-type strain, the Hla mutant strain demonstrated significantly reduced ability to invade corneal epithelial cells in vitro (P < 0.05) and infect murine corneas following total epithelial debridement in vivo (P < 0.05). In conclusion, S. aureus alpha-hemolysin plays a major role in the pathologic modulation of corneal epithelial wound healing and the intracellular invasion of the bacteria. Limiting colonization by S. aureus and/or blocking alpha-hemolysin may provide a therapeutic approach for corneal wound healing and infectious disorders. Highlights: S. aureus α-hemolysin pathologically modulates corneal wound healing in vivo. S. aureus α-hemolysin plays a major role in the intracellular invasion of S. aureus . Murine S. aureus keratitis can be established after total epithelial debridement.