Effect of siderophores on virulence of Neisseria gonorrhoeae.

The virulence of Neisseria gonorrhoeae for chicken embryos can be modified in a predictable manner by the addition of microbial siderophores to the inoculum. "Meningobactin" and "gonobactin," siderophores isolated from iron-limited cultures of meningococci and gonococci, respectively, enhance the virulence of the relatively avirulent colony type 3 (T3) organisms, but have essentially no effect on the virulence of T1 organisms. Both of these compounds were found previously to stimulate in vitro growth of the pathogenic Neisseria spp. under conditions made iron limiting by the addition of conalbumin, the transferrin counterpart of chickens. Similarly, ferrated schizokinen and arthrobactin, both dihydroxamate siderophores which stimulated growth in iron-limited conditions in vitro, also enhanced virulence of T3 organisms, whereas desferrioxamine B mesylate (Desferal), a trihydroxamate previously shown to be inhibitory in vitro, decreased the virulence of the T1 colony form. This was due to the iron-binding function of the molecule, as the iron-saturated form, ferrioxamine B mesylate, did not affect virulence. An additional trihydroxamate siderophore, ferrichrome A, which was inactive on Neisseria spp. in either the deferri- or ferrated forms in vitro, likewise did not affect virulence in the chicken embryo model. The neisserial siderophores were more effective than the other microbial siderophores in enhancing virulence of T3 gonococci. The results add to the evidence that the ability to acquire iron is an important determinant of virulence.