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

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 105 cfu/ml, regardless of the pneumococcal strain. CSF inflammatory changes could be invoked by cisternal instillation of 105−106 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 inflammatio

The Induction of Meningeal Inflammation by Components of the Pneumococcal Cell Wall

Pneumococcal cell wall induces meningeal inflammation in rabbits injected intracisternally with >105 cell equivalents. Both of the major cell wall components, teichoic acid and peptidoglycan, contribute to this inflammatory activity although responses differ depending on the chemical nature, size, and complexity of these fractions. Challenge with teichoic acid (membrane or wall associated) results in greater inflammation at 5 hr than at 24 hr. Degraded teichoic acid is inactive. In contrast, the inflammation caused by whole cell wall or high-molecular-weight peptidoglycan-containing fractions increases in intensity from 5 to 24 hr. Peptidoglycan fractions lose activity at 24 hr when hydrolyzed to disaccharide-stem peptide moieties. Generation of free cell wall components in cerebrospinal fluid as, for example, during treatment with antibiotics that are bacteriolytic as well as bactericidal, could contribute to increased inflammation in the subarachnoid spac

Sequences of rank-1 projections and Gabor tight fusion frames

Abstract from public.pdfThis dissertation provides new results in two areas. The first part concerns the particular properties that are inherited by a sequence of rank-1 projections from the inducing sequence of unit-norm vectors. The second part applies ideas from Gabor analysis for a non-trivial construction of so-called Tight Fusion Frames. The particular necessary conditions such that these Gabor Tight Fusion Frames may perform signal retrieval modulo phase are then investigated

Nonsteroidal Anti-Inflammatory Agents in the Therapy for Experimental Pneumococcal Meningitis

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of the cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhib-itors concurrently with the antibioti

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

A pneumococcal isolate that caused relapsing meningitis in a patient infected with human immunodeficiency virus (HIV) was found to display an unusual response to penicillin - rapid death but a striking lack of cellular lysis. This lytic defect was also detected in all four pneumococcal isolates from three additional HIV-infected patients and in more than half of the clinical isolates from patients with bacteremia. In a rabbit model of meningitis, the lysis-defective strain remained cryptic, with a delay of 5 h in the onset of leukocytosis in cerebrospinal fluid. A marked burst of leukocytosis was associated with ampicillin-induced lysis of a lysis-sensitive strain but not of a lysis-defective strain. Pneumococcal clinical isolates have different lytic responses to penicillin; defective lysis may adversely affect the course of meningitis, an observation suggesting that autolysins play a role in modulating infectious disease

Differences of Pathophysiology in Experimental Meningitis Caused by Three Strains of Streptococcus Pneumoniae

Differences in cytochemical and pathophysiologic abnormalities in experimental meningitis caused by pneumococcal strains A, B, and C were determined. Strain C produced the most severe abnormalities of cerebrospinal fluid (CSF) concentrations of lactate (P < .01), protein (P < .02), and glucose (P < .01), CSF white blood cell count (P < .04), cerebral blood flow (P < .02), and clinical signs (P < .05). Brain edema occurred only with strains A and C, with no association with disease severity; intracranial hypertension was also independent of disease severity. Strain B, not C, achieved the highest bacterial titers in the CSF (P < .005). The widely different abilities of strains of Streptococcus pneumoniae to induce intracranial abnormalities suggest that virulence determinants affect not only evasion of defense during colonization and invasion, as shown in other models, but also determine the course of disease once infection has been established. Differences of cell-wall metabolism among pneumococcal strains may playa role in this latter phase of the development of meningiti