The biologic activities of peptidoglycan in experimental Haemophilus influenzae meningitis.
While gram-positive bacterial cell walls are known to incite inflammation, the contribution of gram-negative peptidoglycan to disease has not been characterized. The ability of cell wall, purified peptidoglycan, and soluble peptidoglycan subcomponents from Haemophilus influenzae to provoke inflammation was determined in a rabbit model of meningitis. Haemophilus peptidoglycan, with or without associated proteins, produced brain edema at > or = 0.1 micrograms/mL of cerebrospinal fluid (CSF); leukocytosis and protein accumulation in CSF occurred only at > or = 10.0 micrograms/mL of CSF. Solubilized peptidoglycan was 10-fold more active than intact cell wall. The bioactivity of peptidoglycan from ampicillin-resistant H. influenzae was at least twofold greater than that of ampicillin-sensitive strains. Consistent with these pathologic effects of purified peptidoglycan, ampicillin-induced bacterial lysates in which endotoxin was neutralized induced brain edema and protein influx but little leukocytosis. Thus, peptidoglycan seems to contribute to the pathology of gram-negative meningitis, particularly brain edema.
Burroughs
M
M
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York, NY 10021.
Prasad
S
S
Cabellos
C
C
Mendelman
P M
PM
Tuomanen
E
E
D000668:Ampicillin Resistance; D000818:Animals; D001929:Brain Edema / Q000382:microbiology*; D002473:Cell Wall / Q000502:physiology; D004195:Disease Models, Animal; D006193:Haemophilus influenzae / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008583:Meningitis, Haemophilus / Q000382:microbiology*; D010457:Peptidoglycan / Q000378:metabolism*; D011817:Rabbits
D010457:Peptidoglycan