title: The molecular pathogenicity of Fusarium keratitis: a fungal transcriptional regulator promotes hyphal penetration of the cornea.
abstract: OBJECTIVE
  The pathogenic mechanisms of fungal infection during human keratomycosis were investigated in an ex vivo corneal model that used strains of Fusarium oxysporum differing in the production of a fungal transcription factor.
  
  
  METHODS
  A pacC loss-of-function mutant and a pacC dominant-activating mutant were constructed from a wild-type isolate of F. oxysporum, and the 3 strains were characterized by in vitro growth kinetics. Twenty-seven human donor corneas maintained in tissue culture were superficially scarified and topically inoculated with the wild-type, the pacC loss-of-function mutant, or the pacC dominant-activating strains. Relative hyphal invasion into the stroma was compared histopathologically in corneal sections.
  
  
  RESULTS
  F. oxysporum strains demonstrated comparable exponential growth rates in vitro. Wild-type F. oxysporum invaded into the corneal tissue within 1 day and penetrated through the anterior stroma during the next 4 days. The pacC loss-of-function mutant invaded explanted corneas significantly less than the wild-type strain on day 1 (P < 0.0001) and on day 3 (P = 0.0003). The pacC dominant-activating strain adhered and penetrated explanted corneas similar to the wild-type strain.
  
  
  CONCLUSIONS
  The PacC pathway regulating the transcription of fungal genes allows fungal adaptation to the ocular surface and enables invasion of the injured cornea by F. oxysporum.
authors.affiliation: Sid W. Richardson Ocular Microbiology Laboratory, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Hua
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Yuan
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Pietro
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Wilhelmus
mesh_terms: D003315:Cornea / Q000382:microbiology*; D003320:Corneal Ulcer / Q000382:microbiology*; D015821:Eye Infections, Fungal / Q000382:microbiology; D005656:Fungal Proteins / Q000235:genetics*; D005670:Fusarium / Q000235:genetics / Q000472:pathogenicity*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D005800:Genes, Fungal / Q000502:physiology; D005838:Genotype; D006801:Humans; D025301:Hyphae / Q000502:physiology*; D008954:Models, Biological; D009181:Mycoses / Q000382:microbiology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors