Project 3 - Antibiotic resistance and metabolic pathways in Chlamydia spp This project will focus on key biosynthetic and metabolic functions of Chlamydia as they impact on drug resistance and growth and survival in the host. It consists of three aims:
Specific Aim 1 - To model the emergence of resistance to the drugs of choice for the treatment of C. trachomatis infections. We will measure the fitness of azithromycin resistant (AZM*^) mutants in vitro and in vivo. We will then screen for compensatory mutants that arise in vivo and characterize these mutants using whole genome sequencing technology. We will also select for spontaneous tetracycline resistant (Tc*^) mutants of C. caviae (GPIC) in a natural infection model in guinea pigs. The mutants that arise in the natural infection setting will be analyzed for growth characteristics such as growth in tissue culture and competition experiments in vivo and in vitro in the absence of antibiotic. A complement to the animal model studies will be a survey for drug resistant Isolates the clinical setting among

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI084044-05
Application #
8527686
Study Section
Special Emphasis Panel (ZAI1-MMT-M)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$392,465
Indirect Cost
$88,326
Name
University of Maryland Baltimore
Department
Type
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Mendes-Soares, Helena; Suzuki, Haruo; Hickey, Roxana J et al. (2014) Comparative functional genomics of Lactobacillus spp. reveals possible mechanisms for specialization of vaginal lactobacilli to their environment. J Bacteriol 196:1458-70
Bavoil, Patrik M (2014) What's in a word: the use, misuse, and abuse of the word "persistence" in Chlamydia biology. Front Cell Infect Microbiol 4:27
Bavoil, Patrik M; Byrne, Gerald I (2014) Analysis of CPAF mutants: new functions, new questions (the ins and outs of a chlamydial protease). Pathog Dis 71:287-91
Hickey, Roxana J; Forney, Larry J (2014) Gardnerella vaginalis does not always cause bacterial vaginosis. J Infect Dis 210:1682-3
Adams, Nancy E; Thiaville, Jennifer J; Proestos, James et al. (2014) Promiscuous and adaptable enzymes fill "holes" in the tetrahydrofolate pathway in Chlamydia species. MBio 5:e01378-14
Brotman, Rebecca M; Ravel, Jacques; Bavoil, Patrik M et al. (2014) Microbiome, sex hormones, and immune responses in the reproductive tract: challenges for vaccine development against sexually transmitted infections. Vaccine 32:1543-52
Hovis, Kelley M; Mojica, Sergio; McDermott, Jason E et al. (2013) Genus-optimized strategy for the identification of chlamydial type III secretion substrates. Pathog Dis 69:213-22
Vorimore, Fabien; Hsia, Ru-Ching; Huot-Creasy, Heather et al. (2013) Isolation of a New Chlamydia species from the Feral Sacred Ibis (Threskiornis aethiopicus): Chlamydia ibidis. PLoS One 8:e74823
Yeruva, Laxmi; Spencer, Nicole; Bowlin, Anne K et al. (2013) Chlamydial infection of the gastrointestinal tract: a reservoir for persistent infection. Pathog Dis 68:88-95
Fisher, Derek J; Fernández, Reinaldo E; Maurelli, Anthony T (2013) Chlamydia trachomatis transports NAD via the Npt1 ATP/ADP translocase. J Bacteriol 195:3381-6

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