title: The transferrin receptor expressed by gonococcal strain FA1090 is required for the experimental infection of human male volunteers.
abstract: 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 proteins, 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 gonococcal transferrin-binding proteins have been implicated in transferrin receptor function, TbpA and TbpB. We constructed a gonococcal transferrin receptor mutant without the introduction of additional antibiotic resistance markers and tested its ability to cause experimental urethritis 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 inoculated volunteers. To our knowledge, this is the first experimental demonstration that a bacterial iron acquisition system is an essential virulence factor for human infection.
authors.affiliation: Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, USA. ccornelissen@gems.vcu.edu
authors.forename: C N
authors.initials: CN
authors.lastname: Cornelissen
authors.forename: M
authors.initials: M
authors.lastname: Kelley
authors.forename: M M
authors.initials: MM
authors.lastname: Hobbs
authors.forename: J E
authors.initials: JE
authors.lastname: Anderson
authors.forename: J G
authors.initials: JG
authors.lastname: Cannon
authors.forename: M S
authors.initials: MS
authors.lastname: Cohen
authors.forename: P F
authors.initials: PF
authors.lastname: Sparling
mesh_terms: D005798:Genes, Bacterial; D006069:Gonorrhea / Q000382:microbiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D016296:Mutagenesis; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D011990:Receptors, Transferrin / Q000235:genetics* / Q000502:physiology; D014170:Transformation, Genetic; D014526:Urethritis / Q000382:microbiology*; D014774:Virulence / Q000235:genetics
chemical_list: D011990:Receptors, Transferrin; D007501:Iron