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> *Thesis Defense Announcement
> To:  The George Mason University Community*
>
> *Candidate: Elizabeth McKenney
> Program: Master of Science in Biology
> *
> *Date:   Friday June 17, 2011
> Time:   11:00 a.m.
> Place:  George Mason University, Prince William campus
> 	     Bull Run Hall, Room 247
>  
> Thesis Chair:  Dr. Monique van Hoek
>
> Title: **"Analogs of Fosmidomycin and FR900098 as Antimicrobial Agents"*
>
>   
>
> A copy of the thesis is on reserve in the Johnson Center Library, 
> Fairfax campus.  The thesis will not be read at the meeting, but 
> should be read in advance.
>
> All members of the George Mason University community are invited to 
> attend.
>
>
>             ABSTRACT:
>
> Isoprenoids are involved in many critical cellular functions, such as 
> cell wall and membrane biosynthesis and electron transport.  Plants, 
> fungi, and some bacteria use the methylerythritol phosphate (MEP) 
> pathway to generate isoprenoids.  Since the MEP pathway is absent in 
> animals, enzymes of this pathway are attractive targets for the 
> development of a novel class of antibiotics.  Fosmidomycin and 
> FR900098 are two antibiotics that are potent inhibitors of 
> 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), the enzyme 
> involved in the first committed step of the MEP pathway.  Fosmidomycin 
> is currently in clinical trials to treat infections of /Plasmodium 
> falciparum/, the organism that causes malaria.  Homologs of DXR have 
> been identified in many bacteria, including /F. tularensis, E. coli, 
> P. aeruginosa, B. abortus, /and /M. tuberculosis/.  Fosmidomycin 
> inhibits the purified DXR of /F. tularensis, E. coli, /and /M. 
> tuberculosis/. The goal of this research was to identify and test 
> analogs of fosmidomycin and FR900098 that are more lipophilic, and 
> therefore theoretically able to cross biological membranes more 
> efficiently.  After screening a panel of compounds, we have identified 
> one compound, termed EU195, which can inhibit the growth of 
> /Francisella novicida/.  Fosmidomycin, FR900098, and EU195 can also 
> inhibit the intracellular growth of /F. novicida/ with low 
> cytotoxicity.  These antibiotics can also prolong the survival of 
> /Galleria mellonella/ wax moth caterpillars that have been infected 
> with /F. novicida/.  This research shows that the lipophilic FR900098 
> analog, EU195, may be a promising contribution to current antibiotics, 
> and that further research in this area to improve these compounds 
> would be beneficial.
>
>  ###
>
>