Showing papers by "Ulrich Vogel published in 1999"

Mechanisms of neisserial serum resistance

Abstract: Pathogenic Neisseria use a variety of mechanisms to survive the bactericidal action of the complement system. Serum resistance is a crucial virulence factor for the development of severe meningococcal disease, meningococcal meningitis and disseminated gonococcal infection. Furthermore, local inflammation at the site of gonococcal infection exposes the bacteria to moderate concentrations of complement factors. We review current concepts of neisserial serum resistance with emphasis on porins and polysaccharides exposed on the neisserial surface and their interaction with components of normal human serum.

Role of Lipopolysaccharide Sialylation in Serum Resistance of Serogroup B and C Meningococcal Disease Isolates

Abstract: α-2,3-Sialyltransferase mutants of three genetically and phenotypically diverse Neisseria meningitidis strains were compared with regard to resistance to human serum and systemic spread in the infant rat. Lipopolysaccharide sialylation was found to be of minor importance for the resistance of serogroup B and C meningococcal disease isolates to complement attack.

Endothelial adhesion molecule expression and its inhibition by recombinant bactericidal/permeability-increasing protein are influenced by the capsulation and lipooligosaccharide structure of Neisseria meningitidis.

Abstract: Vascular endothelial injury is responsible for many of the clinical manifestations of severe meningococcal disease. Binding and migration of activated host inflammatory cells is a central process in vascular damage. The expression and function of adhesion molecules regulate interactions between leukocytes and endothelial cells. Little is known about how meningococci directly influence these receptors. In this study we have explored the effect of Neisseria meningitidis on endothelial adhesion molecule expression and found this organism to be a potent inducer of the adhesion molecules CD62E, ICAM-1, and VCAM-1. Exposure of endothelium to a serogroup B strain of Neisseria meningitidis, B1940, and a range of isogenic mutants revealed that lipooligosaccharide (LOS) structure and capsulation influence the expression of adhesion molecules. Following only a brief exposure (15 min) to the bacteria, there were large differences in the capacity of the different mutants to induce vascular cell adhesion molecules, with the unencapsulated and truncated LOS strains being most potent (P < 0.05). Furthermore, the pattern of cell adhesion molecule expression was different with purified endotoxin from that with intact bacteria. Meningococci were more potent stimuli of CD62E expression than was endotoxin, whereas endotoxin was at least as effective as meningococci in inducing ICAM-1 and VCAM-1. The effect of bactericidal/permeability increasing protein (rBPI(21)), an antibacterial molecule with antiendotoxin properties, was also dependent on LOS structure. The strains which possessed a truncated or nonsialylated LOS, whether capsulated or not, were more sensitive to the inhibitory effects of rBPI(21). These findings could have important implications for the use of antiendotoxin therapy in meningococcal disease.

Infant Rat Model of Acute Meningitis

Abstract: Publisher Summary This chapter focuses on the infant rat model of acute meningitis, which has been used for analyzing the efficacy of antibiotic treatment and passive immunization. The infant rats are used for the infection at the age of approximately five days, when they weigh 10–20 g, as significant delay in the time of infection results reduces the rates of infected animals. Bacterial species used in the infant rat model of bacterial meningitis are stored at -70o C in broth with 10% glycerol. From the permanent stocks, the bacteria are streaked on to appropriate agar plates for overnight growth, or an overnight broth culture is performed. The five modes of challenge used in this model are the intraperitoneal route, the intranasal route, oral infection, subcutanous infection, and intracisternal infection. Iron dextran is used to supplement meningococci with iron during systemic spread in the infant rat. Keeping the infants with their mothers during the course of the disease is desirable and if separation is necessary, the animals should be kept warm and given glucose-water by tube to prevent dehydration. The monitoring of the disease includes sampling and analysis of body fluids, post-mortem analysis of organs and tissues, and additional tests such as peripheral blood cell monitoring or behavioral examination of reconvalescent animals.