Glycolipoprotein Cytotoxin from Leptospira interrogans serovar copenhageni

Abstract

Lipopolysaccharide (EPS), 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. A11 extracts also agglutinated mouse erythrocytes but purified LPS was not cytotoxic. Neither GLP nor LPS were pyrogenic but both gelled Lzmulus amoebocyte lysatc. Specific anti-GLP IgG neutralized the cytotoxic and haemagglutinating effect of GLP ; however, at higher concentrations it enhanced the cytotoxicity of GLP and mediated iysis of the erythrocytes. A high dose of leptospires (ix. organisms) killed weanling mice causing pathological changes similar to those seen in acute Ieptospirosis. 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.

Antigens recognized by the human immune response to severe leptospirosis in Barbados

“…Most of the outer envelope proteins and the low MW carbohydrate antigen were shown to be cross-reactive antigens, of which the low MW carbohydrate antigen may be useful in an early genus-reactive diagnostic test. As LPS elicits opsonic and protective antibodies [13,[27][28][29]30], lacks endotoxic activity [31] and has been shown to be a major protective antigen involved in the human antibody response to infection with other leptospiral serovars [7,9], LPS components may be useful as immunizing agents. Studies are currently being undertaken to further define the components of LPS and other antigens involved in the immune response to infection with leptospires.…”

Cytotoxic activity and probable apoptotic effect of Sph2, a sphigomyelinase hemolysin from Leptospira interrogans strain Lai

“…With respect to the cytotoxicity of virulence factors produced by pathogenic leptospirea, glycolipoprotein fraction from L. interrogans was shown to be cytotoxic to mouse fibroblast cultures (1) and administration of lipopolysaccharide from L. interrogans induced apoptosis of lymphocytes in mice (1). On the other hand, the potential cytotoxic property of hemolysins, an important group of virulence factors widely produced by L. interrogans, is yet to be elucidated.…”

Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin

“…The glycolipoprotein endotoxin was extracted from Leptospira icterohaemorrhagiae copenhageni (a gift from Prof. J. Andrade, Fiocruz, Rio de Janeiro, Brazil) according to the procedure of Braun and Wolff (11) modified by Vinh et al (12). After lyophilization, GLP was dissolved in distilled water and the protein content of the preparation was determined by the Bradford method (13) using Bio-Rad reagents and bovine serum albumin (BSA) as standard.…”