Summary auto-generated
This study investigated toxic components from Leptospira interrogans serovar copenhageni, focusing on a glycolipoprotein (GLP) complex. Researchers extracted and tested GLP, lipopolysaccharide (LPS), and lipid fractions from leptospires using mouse fibroblast cell cultures and other biological assays. GLP and lipid extracts proved cytotoxic to cultured mouse fibroblast cells, with toxicity measured by lactate dehydrogenase leakage. Individual fatty acids (particularly palmitoleic and oleic acids) from leptospiral lipids also showed cytotoxic and hemagglutinating activity. In contrast, purified LPS was not cytotoxic. Specific anti-GLP antibodies neutralized both cytotoxic and hemagglutinating effects at low concentrations but enhanced cytotoxicity at higher concentrations. Neither GLP nor LPS proved pyrogenic in rabbits, though both reacted with Limulus lysate. High doses of live or killed leptospires (both virulent and saprophytic strains) caused lethal infection in mice with pathological changes resembling acute leptospirosis. The results indicate that lipid components, particularly in the GLP complex, contribute to leptospiral toxicity and likely play a role in the pathogenesis of acute leptospirosis.
Key findings
- Glycolipoprotein (GLP), not lipopolysaccharide (LPS), extracted from L. interrogans serovar copenhageni was the primary cytotoxic component to cultured mouse fibroblasts.
- Fatty acids within leptospiral lipids, especially palmitoleic and oleic acids, demonstrated both cytotoxic and hemagglutinating activity against mouse cells and erythrocytes.
- Specific anti-GLP IgG antibodies neutralized cytotoxic effects at low concentrations but enhanced toxicity at higher concentrations, suggesting immune complex involvement.
- Both virulent and non-pathogenic leptospire strains were lethal to mice at high doses (≥10¹⁰ organisms), indicating toxicity is separate from virulence factors.
- Neither GLP nor LPS was pyrogenic in rabbits despite their ability to react with Limulus lysate, suggesting endotoxin-like but non-pyrogenic toxic properties.
This summary was generated automatically from the article PDF and is not part of the original publication. Refer to the PDF for the authoritative text.
Abstract
SUMMARY: Lipopolysaccharide (LPS), glycolipoprotein (GLP) and lipid extract were prepared from Leptospira interrogans serovar copenhageni. GLP, lipid extract or purified fatty acids from lipid extract produced cytotoxic effects seen as cell enzyme leakage followed by cytotoxic death when tested in mouse fibroblast L929 cells in tissue culture. All extracts also agglutinated mouse crythrocytes but purified LPS was not cytotoxic. Neither GLP nor LPS were pyrogenic but both gelled Limulus amoebocyte lysate. Specific anti-GLP IgG neutralized the cytotoxic and haemagglutinating effect of GLP; however, at higher concentrations it enhanced the cytotoxicity of GLP and mediated lysis of the erythrocytes. A high dose of leptospires (i.e. 1010 organisms) killed weanling mice causing pathological changes similar to those seen in acute leptospirosis. Similar results were obtained with live, dead, pathogenic and saprophytic leptospires. The results suggest that toxicity is involved in leptospiral infection and that lipid components either of whole leptospires or of a leptospiral GLP may contribute to the pathogenesis of acute leptospirosis.