THE TRANSFERRIN RECEPTOR EXPRESSED BY GONOCOCCAL STRAIN FA1090 IS REQUIRED FOR THE EXPERIMENTAL-INFECTION OF HUMAN MALE-VOLUNTEERS

Iron, an essential nutrient for most microorganisms, is sequestered by the host to decrease the concentration of iron available to bacterial pathogens. Neisseria gonorrhoeae, the causative agent of gonorrhoea, can acquire iron by direct interaction with human iron-binding protein s, including the serum glycoprotein, transferrin. Iron internalization from host transferrin requires the expression of a bacterial receptor , which specifically recognizes the human form of transferrin. Two gon ococcal transferrin-binding proteins have been implicated in transferr in receptor function, TbpA and TbpB. We constructed a gonococcal trans ferrin receptor mutant without the introduction of additional antibiot ic resistance markers and tested its ability to cause experimental ure thritis in human male volunteers. The transferrin receptor mutant was incapable of initiating urethritis, although the same inoculum size of the wild-type parent strain, FA1090, causes urethritis in >90% of ino culated volunteers. To our knowledge, this is the first experimental d emonstration that a bacterial iron acquisition system is an essential virulence factor for human infection.