The molecular pathogenicity of Fusarium keratitis: a fungal transcriptional regulator promotes hyphal penetration of the cornea.
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.
Hua
Xia
X
Sid W. Richardson Ocular Microbiology Laboratory, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA.
Yuan
Xiaoyong
X
Di Pietro
Antonio
A
Wilhelmus
Kirk R
KR
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*
D005656:Fungal Proteins; D014157:Transcription Factors