Implication of pneumolysin as a virulence factor in Streptococcus pneumoniae endophthalmitis.
OBJECTIVE
To determine if pneumolysin, a multifunctional cytotoxin produced by Streptococcus pneumoniae, may be a virulence determinant in the pathogenesis of pneumococcal endophthalmitis.


METHODS
Lewis rats (n = 20) were injected intravitreally with purified recombinant pneumolysin at the following doses; 3.9 hemolytic units (HU), 39 HU, 390 HU, 3.9 x 10(3) HU, and 3.9 x 10(4) HU. After 24 hours, eyes were examined clinically and enucleated for histopathologic examination to elucidate the dose-response relationship. To determine the temporal progression of the disease model, a second group of rats (n = 8) were injected intravitreally with 390 HU of pneumolysin. At 6 and 48 hours, eyes were examined clinically and enucleated for histopathology.


RESULTS
Eyes injected with pneumolysin demonstrated increasing anterior and posterior segment inflammation in response to increasing doses of administered toxin. The onset of inflammation and tissue damage occurred rapidly, and was maximal at 24 to 48 hours. The clinical and histopathologic changes observed mimicked those of S. pneumoniae endophthalmitis. Histopathologic analysis demonstrated rapid onset of iridocyclitis and vitritis with polymorphonuclear leukocyte influx, inner retinal necrosis, and retinal detachment. Retinal pigment epithelial necrosis and choroiditis were noted at the highest doses administered. Inflamed eyes were shown to be sterile.


CONCLUSIONS
Pneumolysin injected intravitreally induces many of the clinical and histopathologic features of pneumococcal endophthalmitis, and may play an important role in the inflammation and tissue damage that occurs in pneumococcal endophthalmitis.
Ng
E W
EW
Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114-3096, USA.
Samiy
N
N
Rubins
J B
JB
Cousins
F V
FV
Ruoff
K L
KL
Baker
A S
AS
D'Amico
D J
DJ
D000818:Animals; D001426:Bacterial Proteins; D003603:Cytotoxins / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D009877:Endophthalmitis / Q000382:microbiology* / Q000473:pathology; D015818:Eye Infections, Bacterial / Q000382:microbiology* / Q000473:pathology; D007267:Injections; D008297:Male; D011008:Pneumococcal Infections / Q000382:microbiology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D013296:Streptococcus pneumoniae / Q000378:metabolism / Q000472:pathogenicity*; D013301:Streptolysins / Q000494:pharmacology*; D014774:Virulence / Q000187:drug effects; D014822:Vitreous Body
D001426:Bacterial Proteins; D003603:Cytotoxins; D011994:Recombinant Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae