The Relative Role of Bacterial Cell Wall and Capsule in the Induction of Inflammation in Pneumococcal Meningitis

Abstract

The relative contribution of bacterial components to the induction of inflammation during Streptococcus pneumoniae meningitis is unknown. Several strains of pneumococci with differences in cell surface characteristics (capsule or cell wall) were compared for the effect on the inflammatory response evoked during infection of the cerebrospinal fluid (CSF) in vivo. The presence of bacterial capsular polysaccharide was not necessary for bacterial growth in CSF in vivo but correlated with greater CSF bacterial density. CSF inflammatory changes began to appear when the bacterial concentration exceeded 10 5 cfu/ml, regardless of the pneumococcal strain. CSF inflammatory changes could be invoked by cisternal instillation of 10 5-106 cell equivalents of whole, heat-killed unencapsulated strains or their isolated cell walls but not by similar concentrations of heat-killed encapsulated strains or isolated capsular polysaccharide. Hypoglycorrhachia was observed only during inflammation caused by live bacteria. The inflammatory response characteristic of naturally acquired pneumococcal meningitis can be reproduced by challenge with both encapsulated and unencapsulated bacteria. The bacterial cell wall appears to be the most potent pneumococcal surface component in inducing CSF inflammation.

Microbiological and Clinical Significance of a New Property of Defective Lysis in Clinical Strains of Pneumococci

“…Continued growth of the lysis-defective strain did not result in increasing CSF leukocytosis. The onset of leukocytosis in CSF has occurred between 0.7 and 1 x 10 6 cfu/mL for all pneumococci tested thus far, regardless of capsular type [10]. Thus, a delay of 5 h and an increase in the bacterial density to >10 7 cfu/mL before the onset of leukocytosis for the lysis-defective strain is an important result.…”

“…The cryptic nature of infection with the lysisdefective strain would contribute to higher morbidity and mortality from this type of infection. It is known that antibiotic-induced lysis and subsequent release of cell wall-degradation products contribute to generating inflammation in the CNS and the lung [10,16,17]. By this criterion, the lysis-defective strains would be expected to generate less inflammation, particularly during antibiotic-induced cell death in vivo.…”

“…Groups of four rabbits were anaesthetized and placed in stereotaxic frames as previously described [9,10]. Pneumococcal strains SIll and Br were grown to logarithmic phase in C +Y medium, washed, and resuspended in pyrogen-free saline at a concentration of 10 3 cfu in 0.2 mL.…”

“…After removal of 0.3 mL of CSF, the preparations were instilled into the cisterna magna. Cytochemical determinations of CSF were repeated in each animal over a 24-h period to document changes in the density of leukocytes and the concentrations of glucose, protein, and lactic acid [10]. Bacterial titers in CSF were determined on tryptic-soy agar containing 3% sheep blood.…”

“…The lysis-sensitive strain Sur has been studied extensively in the rabbit model of meningitis [9,10]. We compared the growth rate, the onset of CSF abnormalities, and the response to ampicillin of strain Sui with that of the lysis-defective strain Br.…”