The limited role of pneumolysin in the pathogenesis of pneumococcal meningitis.
The aim of this study was to determine the role of pneumolysin, an intracellular toxin of Streptococcus pneumoniae, in the pathogenesis of pneumococcal meningitis. Recombinant pneumolysin (1 microgram), when injected intracisternally into rabbits, resulted in a brisk inflammatory response. However, a pneumolysin-deficient strain of S. pneumoniae caused meningeal inflammation in rabbits indistinguishable from that induced by the parent pneumolysin-producing strain. Furthermore, similar enhancement of meningeal inflammation occurred after ampicillin therapy in animals infected with either the parent strain or the pneumolysin-deficient mutant. These results suggest that although pneumolysin can stimulate the inflammatory cascade in the central nervous system, it is not necessary for the pathogenesis of meningeal inflammation nor does it play a role in postantibiotic enhancement of meningeal inflammation.
Friedland
I R
IR
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, USA.
Paris
M M
MM
Hickey
S
S
Shelton
S
S
Olsen
K
K
Paton
J C
JC
McCracken
G H
GH
D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D001426:Bacterial Proteins; D002556:Cerebrospinal Fluid Proteins / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D007249:Inflammation; D007773:Lactates / Q000134:cerebrospinal fluid; D007962:Leukocytes / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000382:microbiology / Q000503:physiopathology*; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity; D013296:Streptococcus pneumoniae / Q000302:isolation & purification / Q000472:pathogenicity*; D013301:Streptolysins / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
D001426:Bacterial Proteins; D002556:Cerebrospinal Fluid Proteins; D003603:Cytotoxins; D007773:Lactates; D011994:Recombinant Proteins; D013301:Streptolysins; D014409:Tumor Necrosis Factor-alpha; C032290:plY protein, Streptococcus pneumoniae; D000667:Ampicillin