image: Dr. Cynthia Nau Cornelissen, Distinguished University Professor and director of the Center for Translational Immunology in the Institute for Biomedical Sciences at Georgia State University view more
Credit: Georgia State University
ATLANTA—Dr. Cynthia Nau Cornelissen, Distinguished University Professor and director of the Center for Translational Immunology in the Institute for Biomedical Sciences at Georgia State University, has received a five-year, $4.9 million federal grant to study ways to block the bacterial pathogen Neisseria gonorrhoeae from causing gonorrhea, a common sexually transmitted infection.
The grant from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases will explore N. gonorrhoeae metal transporters that disrupt nutritional immunity, a human process that prevents microbial growth and infectivity by limiting the availability of critical nutrients, such as the metals iron and zinc, and starving invading pathogens.
This project will test whether N. gonorrhoeae disrupts nutritional immunity by deploying outer membrane transporters that bind to and relieve the host’s metal-binding proteins of the metal cargo they have sequestered. The researchers propose that N. gonorrhoeae can cause gonorrhea infection by hijacking human immunity proteins and stripping them of metals.
Gonorrhea, rates of which are increasing worldwide, is a public health threat because of growing incidence of antimicrobial drug resistance, rising treatment costs and lack of a protective vaccine. Many cases in women are asymptomatic, and if left untreated, gonorrhea can lead to serious health consequences, including pelvic inflammatory disease, ectopic pregnancy, infertility and life-threatening conditions including disseminated gonococcal infections.
“We hypothesize that these metal transporters enable N. gonorrhoeae to overcome the growth inhibitory effects of the innate immunity proteins produced during inflammation,” Cornelissen said. “These studies are significant because knowing how N. gonorrhoeae acquires essential metals like zinc and iron from the human host opens new opportunities for developing new therapeutics against ‘superbug’ strains, whether they be targets for a protective vaccine or small molecule inhibitors of crucial transporters.”
The proposed studies will shed new light on fundamental pathogenic mechanisms used by N. gonorrhoeae to overcome nutritional immunity imposed by the human host. The project seeks to understand the structure and function relationships in four outer membrane transporters produced by N. gonorrhoeae during infection of relevant host cells.
The researchers will explore whether inhibitory compounds or monoclonal antibodies block these critical metal acquisition functions, which can point to new therapies against this common infectious disease.
For more information about the grant, visit https://reporter.nih.gov/search/_7BdQ7MAZkqTuw40zk4quA/project-details/10585577.