Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Staphylococcus aureus produces a variety of proteins, including alpha-toxin and protein A, that could contribute to corneal tissue damage during keratitis. We examined corneal infections produced by intrastromal injection of four S. aureus strains--three isogenic mutants, one lacking alpha-toxin (Hly- Spa+), one lacking protein A (Hly+ Spa-), and one lacking both alpha-toxin and protein A (Hly- Spa-), and the wild type (Hly+ Spa+)--in a rabbit model of experimental keratitis. Rabbit corneas were injected intrastromally with 100 CFU of one of the four strains, and the eyes were examined by slit lamp biomicroscopy over a 25-h period. Corneal homogenates were used for determination of CFU and neutrophil myeloperoxidase activity at 5-h intervals. All strains had the same logarithmic growth curve from 0 to 10 h postinfection, after which CFU remained constant at 10(7) CFU per cornea. By 15 h postinfection, slit lamp examination scores were significantly higher for eyes infected with Hly+ strains than for Hly(-)-infected eyes. At this time, distinct epithelial erosions were seen in Hly(+)-infected eyes but not in Hly(-)-infected eyes. Myeloperoxidase activity was significantly greater for Hly(+)-infected corneas than for Hly(-)-infected corneas at both 20 and 25 h postinfection. Spa(+)- and Spa(-)-infected eyes showed no differences in slit lamp examination scores or myeloperoxidase activities. These results suggest that alpha-toxin, but not protein A, is a major virulence factor in staphylococcal keratitis, mediating the destruction of corneal tissue in eyes infected with this bacterial pathogen.
 ...
PMID:Corneal virulence of Staphylococcus aureus: roles of alpha-toxin and protein A in pathogenesis. 818 73

Keratitis caused by Pseudomonas aeruginosa is a potentially vision-threatening condition that requires prompt treatment to prevent vision loss. The recognition of infectious agents by the Toll-like receptor (TLR) system initiates primary innate and later adaptive immune responses. In this study, in late cases of corneal P. aeruginosa infection, the expression of TLR2, 4, 5 and 9 mRNA were all upregulated. In early infection cases, only TLR9 mRNA expression was upregulated. In late cases, the protein expression of TLR2, 4, 5, 9 and pIkappaB-alpha were elevated. In early cases, only TLR9 and pIkappaB-alpha expression were upregulated. Concentrations of IL-6 and IL-8 increased in infected corneas, especially in late cases. Myeloperoxidase (MPO) activity suggested that polymorphonuclear leukocyte (PMN) numbers were higher in late than in early stages of infection. The delayed response of TLRs may explain why P. aeruginosa infection exacerbates rapidly at the early infection stage. This finding may have important implications for the treatment of innate immunologic responses to corneal infections.
 ...
PMID:The delayed response of Toll-like receptors may relate to Pseudomonas aeruginosa keratitis exacerbating rapidly at the early stages of infection. 2001 80