Ability of gonococcal and meningococcal lipooligosaccharides to clot Limulus amebocyte lysate

Roth, Randy S.; Yamasaki, Ryohei; Mandrell, Robert E.; Griffiss, J. McLeod

doi:10.1128/iai.60.3.762-767.1992

Cited by 23 publications

(5 citation statements)

References 38 publications

(24 reference statements)

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“…However, it has been established that the LAL assay is not a reliable method for predicting differences between neisserial strains in host responses. 18 The well-known range in endotoxin and cytokine concentrations found in patients with meningococcal disease 7,19 is thus determined not only by individual endotoxin responsiveness of the host and bacterial numbers, but possibly, also by the properties of the bacterial strain involved.…”

Section: Discussionmentioning

confidence: 99%

No increase in endotoxin release during antibiotic killing of meningococci

Prins

Speelman²,

Kuijper³

et al. 1997

Journal of Antimicrobial Chemotherapy

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Endotoxin is liberated following antibiotic killing of Gram-negative rods, and antibiotics may differ in this respect. Although the amount of filterable endotoxin has also been reported to increase following antibiotic killing of meningococci, it is unknown how this influences the host response. We investigated the influence of three antibiotics on levels of free endotoxin in culture medium and cytokine production in whole blood ex vivo during killing of four strains of meningococci. Bacterial killing was significantly more efficient with penicillin or ceftriaxone than with chloramphenicol, and free endotoxin levels were lower after exposure to antibiotics as compared with no treatment (ANOVA, P < 0.001). Endotoxin levels were lowest after exposure to chloramphenicol. In three of the four strains exposure to antibiotics resulted in considerably lower cytokine levels (ANOVA, P < 0.001), and TNF-alpha levels were significantly lower after exposure to penicillin or ceftriaxone than after chloramphenicol treatment. Only in the strain that induced the lowest levels of TNF-alpha were cytokine levels comparable for untreated and treated samples. We conclude that fear of excessive endotoxin release or cytokine production caused by effective antibiotics is not justified in the treatment of meningococcal infections.

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Section: Discussionmentioning

confidence: 99%

No increase in endotoxin release during antibiotic killing of meningococci

Prins

Speelman²,

Kuijper³

et al. 1997

Journal of Antimicrobial Chemotherapy

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“…45 LPSs from different strains vary in the ability to activate the Limulus amebocyte lysate (LAL) assay suggesting structural heterogeneity of lipid A between strains. 46 The toxicity of outer membrane vesicles Native meningococcal blebs are potent activators of human monocytes and whole blood, and are even more potent than purified meningococcal LPS in activating the LAL assay. 35 Outer membrane vesicles produced from the N. meningitidis serogroup B (H44/76) strain and infused intravenously for 1 h induced 37.5% and 44% mortality in young piglets and older pigs, respectively.…”

Section: Toxicity Of N Meningitidis Lpsmentioning

confidence: 99%

Invited review: Neisseria meningitidis lipopolysaccharides in human pathology

Brandtzæg

Bjerre

Øvstebø

et al. 2001

Journal of Endotoxin Research

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Neisseria meningitidis causes meningitis, fulminant septicemia or mild meningococcemia attacking mainly children and young adults. Lipopolysaccharides (LPS) consist of a symmetrical hexa-acyl lipid A and a short oligosaccharide chain and are classified in 11 immunotypes. Lipid A is the primary toxic component of N. meningitidis. LPS levels in plasma and cerebrospinal fluid as determined by Limulus amebocyte lysate (LAL) assay are quantitatively closely associated with inflammatory mediators, clinical symptoms, and outcome. Patients with persistent septic shock, multiple organ failure, and severe coagulopathy reveal extraordinarily high levels of LPS in plasma. The cytokine production is compartmentalized to either the circulation or to the subarachnoid space. Mortality related to shock increases from 0% to > 80% with a 10-fold increase of plasma LPS from 10 to 100 endotoxin units/ml. Hemorrhagic skin lesions and thrombosis are caused by up-regulation of tissue factor which induces coagulation, and by inhibition of fibrinolysis by plasminogen activator inhibitor 1 (PAI-1). Effective antibiotic treatment results in a rapid decline of plasma LPS (half-life 1-3 h) and cytokines, and reduced generation of thrombin, and PAI-1. Early antibiotic treatment is mandatory. Three intervention trials to block lipid A have not significantly reduced the mortality of meningococcal septicemia.

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“…However, monophosphoryl enteric lipid A is less bioactive than diphosphoryl lipid A, as shown by the rabbit pyrogenicity test, the chicken embryo lethal dose test, and the Schwartzmann reaction, as well as by a reduced ability to stimulate monokine induction in murine macrophage cell lines (46). Indeed, a brief study of the ability of meningococcal and gonococcal LOS to clot Limulus amebocyte lysate revealed that this activity was strain dependent and possibly related to the amount of phosphorylated lipid A expressed by each isolate (49). The biological importance of phosphorylation of meningococcal lipid A remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

The (α2→8)-Linked Polysialic Acid Capsule and Lipooligosaccharide Structure Both Contribute to the Ability of Serogroup BNeisseria meningitidisTo Resist the Bactericidal Activity of Normal Human Serum

Kahler

Martin²,

Shih³

et al. 1998

Infect Immun

143

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The molecular basis for the resistance of serogroup BNeisseria meningitidis to the bactericidal activity of normal human sera (NHS) was examined with a NHS-resistant, invasive serogroup B meningococcal isolate and genetically and structurally defined capsule-, lipooligosaccharide (LOS)-, and sialylation-altered mutants of the wild-type strain. Expression of the (α2→8)-linked polysialic acid serogroup B capsule was essential for meningococcal resistance to NHS. The very NHS-sensitive phenotype of acapsular mutants (99.9 to 100% killed in 10, 25, and 50% NHS) was not rescued by complete LOS sialylation or changes in LOS structure. However, expression of the capsule was necessary but not sufficient for a fully NHS-resistant phenotype. In an encapsulated background, loss of LOS sialylation by interrupting the α2,3 sialyltransferase gene,lst, increased sensitivity to 50% NHS. In contrast, replacement of the lacto-N-neotetraose α-chain (Galβ1-4GlcNAcβ1-3Galβ1-4Glc) with glucose extensions (GlcN) in a galE mutant resulted in a strain resistant to killing by 50% NHS at all time points. Encapsulated meningococci expressing a Hep2(GlcNAc)→KDO2→lipid A LOS without an α-chain demonstrated enhanced sensitivity to 50% NHS (98% killed at 30 min) mediated through the antibody-dependent classical complement pathway. Encapsulated LOS mutants expressing truncated Hep2→KDO2→lipid A and KDO2→lipid A structures were also sensitive to 50% NHS (98 to 100% killed at 30 min) but, unlike the wild-type strain and mutants with larger oligosaccharide structures, they were killed by hypogammaglobulinemic sera. These data indicate that encapsulation is essential but that the LOS structure contributes to the ability of serogroup B N. meningitidis to resist the bactericidal activity of NHS.

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Ability of gonococcal and meningococcal lipooligosaccharides to clot Limulus amebocyte lysate

Abstract: We investigated whether the striking difference in severity of coagulopathy observed between bacterial sepsis involving Neisseria meningitidis and Neisseria gonorrhoeae species is related to species-dependent abilities to * Corresponding author.

Cited by 23 publications

References 38 publications

No increase in endotoxin release during antibiotic killing of meningococci

No increase in endotoxin release during antibiotic killing of meningococci

Invited review: Neisseria meningitidis lipopolysaccharides in human pathology

The (α2→8)-Linked Polysialic Acid Capsule and Lipooligosaccharide Structure Both Contribute to the Ability of Serogroup BNeisseria meningitidisTo Resist the Bactericidal Activity of Normal Human Serum

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