The overall goal of the Mouse Infection Core (Core B) is to conduct animal infection experiments for other researchers in the Atlantic Coast STI CRC using mouse models of Neisseria gonorrhoeae (Ng) and Ng/Chlamydia muridarum (Cm) coinfection developed by our laboratory. Core B is a key integrative component for reaching the Center's long-term goals and thus, this core is critical to the success of the Center. Core B will provide services for at least two research projects in our group (Project 3, Cornelissen) and Project 5 (Nicholas/Shafer) and to other Center investigators who need our expertise. Having a Research Core for this purpose is highly beneficial to the Center in that it allows experiments to be conducted in the same manner between labs, and thus standardizes results. It also allows research to proceed in an efficient and cost-effective manner. For some Center projects, the Ng/Cm coinfection model will be performed in the PI's laboratory due to the sophistication of the assays used to measure desired responses or the need to use mice that are not commercially available (Project 1, Duncan;Project 2, Fields). The coinfection model, which was only recently developed, is technically complicated and it is important that our Center has a mechanism for coordinating its use since understanding STI coinfections is one of the main objectives of our Center. We will therefore train individuals in these laboratories as needed. To accomplish the goals of Core B, we have organized our services under the following specific aims:
Aim 1) Microbial fitness studies: We will conduct competitive infections to measure the relative fitness of mutant and wild-type Ng strains in the lower genital tract of female mice;
Aim 2) Pathogenesis studies: We will conduct noncompetitive infections to study whether certain Ng factors are required for infection and the impact of these factors on the mouse response to Ng;
Aim 3) Coinfection studies: We will test Ng mutants in mice that have a Cm infection to determine whether the in vivo phenotypes of the mutants, disease progression, and host responses are altered in the context of coinfection;
Aim 4) : Product development: We will perform immunization and challenge studies with candidate Ng vaccines in the Ng and Ng/Cm infecton models. Should progress by any of Center PIs lead to potential therapeutic treatments (e.g. novel antimicrobials, immunotherapies), we can also test the in vivo efficacy of these candidate products in either model using well-established protocols;
Aim 5) : Consultation and training: We will provide technical advice, assist with experimental designs, and perform hands-on training with other Center PIs and technical staff as needed.

Public Health Relevance

Over 200 million cases of Neisseria gonorrhoeae and sexually transmitted Chlamydia trachomatis infections occur world-wide each year. Concurrent infections are also common, yet little is known about the clinical aspects or pathogenesis of gonococcal/chlamydial coinfection. The goals of the Mouse Infection Core are to conduct mouse infection studies, specifically mouse models of Ng and Ng/Chlamydia coinfection, for other investigators in the Center and to provide training and technical advice as needed. The goals of this Research Core are consistent with the overall goal of the Center by facilitating research on single and dual Ng and Cm infections and the development of novel interventions.

Agency
National Institute of Health (NIH)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI113170-01
Application #
8769565
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
City
Bethesda
State
MD
Country
United States
Zip Code
20817