Comparison of the abilities of different protein sources of iron to enhance Neisseria meningitidis infection in mice

Abstract

This study was done primarily to determine whether the previously observed specificity of the meningococcal transferrin and lactoferrin receptors for human proteins was maintained in vivo during meningococcal infection in mice. Preliminary experiments evaluating the choice of host strain, the age and sex of mice, and the growth conditions of the meningococci indicated that 45-day-old female Swiss Webster mice challenged with meningococci grown on low-pH, low-iron Mueller-Hinton agar plates were appropriate for this study. The comparison of transferrins and lactoferrins from different species demonstrated that only the human forms of these proteins were utilized by meningococci; there was significantly greater mortality among mice treated with iron-saturated human transferrin or lactoferrin (93 and 100%, respectively) than among those not treated or treated with iron-saturated bovine transferrin or bovine lactoferrin (0%). Provision of exogenous hemoglobin also resulted in increased mortality, although not as great as that observed with amounts of transferrin with equivalent iron content, which parallels the more effective utilization of transferrin and lactoferrin in in vitro growth experiments. In addition, unlike with transferrin and lactoferrin, there was no difference in utilization of human and bovine hemoglobin in vitro or in vivo.

Identification and characterization of a porcine‐specific transferrin receptor in Actinobacillus pleuropneumoniae

“…In this paper we demonstrate that strains of A. pleuropneumoniae are capable of obtaining iron only from porcine transferrin and that iron-deficient cells or membranes from these strains possess specific porcine transferrin binding activity. The failure to detect siderophores in previous preliminary studies (Deneer and Potter, 1989) suggests that, like N. meningitidis (Schryvers and Gonzalez, 1989), A. pieuropneumoniae may be dependent upon a transferrin receptor-mediated iron-uptake system in vivo.…”

“…Polyacrylamide gel electrophoresis, silver staining of gels, and electroblotting were performed essentially as described previously (Schryvers, 1989).…”

“…The importance of bacterial iron-acquisition systems capable of obtaining iron for growth in vivo has been substantiated for several bacterial species {Weinberg, 1978;Crosa, 1984;Schryvers and Gonzalez. 1989) but very little is known about iron-acquisition mechanisms in A. pieuropneumoniae.…”

A mouse model utilising human transferrin to study protection against Neisseria meningitidis serogroup B induced by outer membrane vesicle vaccination

“…Meningococci express an array of iron-regulated surface accessible receptors that mediate speci¢c binding and uptake of di¡erent iron containing proteins from the host of which transferrin is the most important [18]. A prerequisite for a relevant e¡ect of exogenous human transferrin in the model system was, therefore, to challenge with meningococci grown under iron restriction to up-regulate the expression of the transferrin receptors [15,16,18]. By studying the in vitro growth of meningococci in the presence of increasing amounts of the Fe 2 chelator EDDA, we were able to determine the optimal concentration of the chelator (60 WM) that should be used to obtain challenge bacteria which fully utilise human transferrin for their growth.…”

“…A prerequisite for a relevant e¡ect of human transferrin in the model system is that the challenge bacteria can utilise this source of iron through speci¢c binding and uptake by the transferrin receptor [141 6]. Since the surface expression of the transferrin receptor is up-regulated in the absence of iron [15,16,18], we ¢rst determined the culture conditions required to obtain bacterial growth under iron re- striction. Parallel bacterial cultures were inoculated in BHI medium in the presence of increasing concentrations of EDDA (Fe 2 chelator) and the growth was monitored continuously by measurement of optical density (OD 600 ) for 11 h. The results, shown in Fig.…”