Staphylococcus aureus alpha-hemolysin impairs corneal epithelial wound healing and promotes intracellular bacterial invasion.
Animals
Corneal Diseases
/ microbiology
Disease Models, Animal
Epithelial Cells
/ microbiology
Epithelium, Corneal
/ injuries
Hemolysin Proteins
/ physiology
Humans
Keratitis
/ microbiology
Mice
Mice, Inbred C57BL
Staphylococcal Infections
/ microbiology
Staphylococcus aureus
/ pathogenicity
Wound Healing
/ physiology
Alpha-hemolysin
Alpha-toxin
Cornea
Infection
Keratitis
Staphylococcus aureus
Wound healing
Journal
Experimental eye research
ISSN: 1096-0007
Titre abrégé: Exp Eye Res
Pays: England
ID NLM: 0370707
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
07
08
2018
revised:
20
02
2019
accepted:
21
02
2019
pubmed:
2
3
2019
medline:
14
2
2020
entrez:
2
3
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30822400
pii: S0014-4835(18)30592-X
doi: 10.1016/j.exer.2019.02.019
pmc: PMC6447303
mid: NIHMS1523140
pii:
doi:
Substances chimiques
Hemolysin Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
263-270Subventions
Organisme : NEI NIH HHS
ID : K12 EY021475
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY001792
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024349
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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