The Iron-Repressed, AraC-Like Regulator MpeR Activates Expression offetAin Neisseria gonorrhoeae

Author:

Hollander Aimee,Mercante Alexandra Dubon,Shafer William M.,Cornelissen Cynthia Nau

Abstract

ABSTRACTNeisseria gonorrhoeaeis an obligate human pathogen that causes the common sexually transmitted infection gonorrhea. Gonococcal infections cause significant morbidity, particularly among women, as the organism ascends to the upper reproductive tract, resulting in pelvic inflammatory disease, ectopic pregnancy, and infertility. In the last few years, antibiotic resistance rates have risen dramatically, leading to severe restriction of treatment options for gonococcal disease. Gonococcal infections do not elicit protective immunity, nor is there an effective vaccine to prevent the disease. Thus, further understanding of the expression, function, and regulation of surface antigens could lead to better treatment and prevention modalities in the future. In the current study, we determined that an iron-repressed regulator, MpeR, interacted specifically with the DNA sequence upstream offetAand activated FetA expression. Interestingly, MpeR was previously shown to regulate the expression of gonococcal antimicrobial efflux systems. We confirmed that the outer membrane transporter FetA allows gonococcal strain FA1090 to utilize the xenosiderophore ferric enterobactin as an iron source. However, we further demonstrated that FetA has an extended range of substrates that encompasses other catecholate xenosiderophores, including ferric salmochelin and the dimers and trimers of dihydroxybenzoylserine. We demonstrated thatfetAis part of an iron-repressed, MpeR-activated operon which putatively encodes other iron transport proteins. This is the first study to describe a regulatory linkage between antimicrobial efflux and iron transport inN. gonorrhoeae. The regulatory nidus that links these systems, MpeR, is expressed exclusively by pathogenic neisseriae and is therefore expected to be an important virulence factor.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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