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      • Small-Molecule inhibition of Siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis

        Julian A Ferreras,Ryu, Jae-Sang,Federico Di Lello,Derek S Tan,Luis E N Quadri 이화여자대학교 약학연구소 2005 藥學硏究論文集 Vol.- No.16

        Mycobacterium tuverculosis and Yersinia pestis, the causative agents of tuberculosis and plague respectively are pathogens with serious ongoing impact on global public health^(1,2) and potential use as agents of bioterrorism^(3). Both pathogens have iron acquisition systems based on siderphores secreted iron-chelating compounds with extremey high Fe^(3+)affinity(4,5) Several lines of evidence suggest that siderophores have a critical role in bacterial iron acquisition inside the human host^(6-9) where the free iron concentration is well bellow that required for bacterial growth and virulence ^(10) Thus, siderophore biosynthesis is an attractive target in the development of new antibiotics to treat tuberculosis and plague^(2,5,8,11). In particular, such drugs alone or as part of combination therapies could provide a valuable new line of defense against intractable muliple-drug-resistant infections Here we report the design synthesis and domain salicylation enzymes required for siderophore biosynthesis siderophore biosynthesis and growth of M. tuberculosis and Y, pestis under iron-limiting conditions.

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