Gardnerella promotion of n. Gonorrhoeae pathogenesis

Active Project Grant Awarded Last action

Award ID
R21AI193750
Recipient
Awarding agency
Obligated
$435,313

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 64% complete
Place of performance
Madison, WI 53715, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Neisseria gonorrhoeae is the causative agent of the sexually-transmitted infection gonorrhea and causes serious complications in women, including pelvic inflammatory disease, ectopic pregnancy, and tubal-factor infertility. Gonorrhea is more frequent in women who have bacterial vaginosis (BV). BV is the most common gynecological disorder in women of childbearing age and is associated with adverse pregnancy outcomes and enhanced transmission of sexually-transmitted diseases. We hypothesize that gardnerella promotes n. Gonorrhoeae pathogenesis in ways that affect bacterial survival via immune evasion and ability to infect new hosts via lipooligosaccharide (LOS) sialylation. Two gardnerella virulence factors appear capable of shifting the balance between two mechanisms that impact LOS-dependent infectivity traits of gonococci. First, the cytolytic toxin vaginolysin releases epithelial cell contents in a CD59-dependent manner that promotes LOS sialyation necessary for gonococcal immune evasion through the recruitment of factor h, a negative regulator of complement killing. Second, a sialidase produced by some gardnerella species can remove sialic acid from gonococcal LOS, a step needed to promote transmission via binding to asialyloglycoprotein receptors on endometrial cells and male urethral cells. These factors may act at different points in disease progression, since vaginolysin is predicted to be produced by certain phase variants early in infection, and sialidase is made by different phase variants at a later stage. Although gardnerella SPP. Have not previously been genetically tractable, we developed methods for making targeted, selectable mutations as well as complements in the gardnerella chromosome. We will use mutants of gardnerella, n. Gonorrhoeae, and human cell lines derived from the cervix, uterus, and the male urethra to determine the mechanisms by which gardnerella vaginolysin and sialidase promote immune evasion and dissemination of n. Gonorrhoeae.

Transactions

Action Obligated Date
Amendment $191,563
Original award $243,750

Subawards

Subrecipient Amount Awarded
Ohio University Dr. Weyand will continue collaborative studies with Dr. Dillard to understand Neisseria gonorrhoeae complement evasion mechanisms triggered by Gardnerella… $207,625

Quick answers

Who received award R21AI193750?

R21AI193750 was awarded to University Of Wisconsin System by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 10, 2025.

How much is award R21AI193750 worth?

$435,313 has been obligated on R21AI193750.

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