ISOLATION AND ANALYSIS OF A FUR MUTANT OF NEISSERIA-GONORRHOEAE

The pathogenic Neisseria spp. produce a number of iron-regulated gene products that are thought to be important in virulence. Iron-responsiv e regulation of these gene products has been attributed to the presenc e in Neisseria spp. of the Fur (ferric uptake regulation) protein. Evi dence for the role of Fur in neisserial iron regulation has been indir ect because of the inability to make fur null mutations. To circumvent this problem, we used manganese selection to isolate missense mutatio ns of Neisseria gonorrhoeae fur. We show that a mutation in gonococcal fur resulted in reduced modulation of expression of four well-stained iron-repressed genes and affected the iron regulation of a broad rang e of other genes as judged by two-dimensional polyacrylamide gel elect rophoresis (PAGE). All 15 of the iron-repressed spots observed by two- dimensional PAGE were at least partially derepressed in the fur mutant , and 17 of the 45 iron-induced spots were affected by the fur mutatio n. Thus, Fur plays a central role in regulation of iron-repressed gono coccal genes and appears to be involved in regulation of many iron-ind uced genes. The size and complexity of the iron regulons in N. gonorrh oeae are much greater than previously recognized.