Generation of a Complete Set of Precise Null Bar-Coded Deletion Mutants of Mycobacterium tuberculosis

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Project Abstract Tuberculosis (TB) continues to be a major global health problem with 9 million new cases per year resulting in 1.7 million deaths, due in large part to the HIV epidemic and emergence of multi- and extensively drug resistant TB strains (MDR- and XDR-TB) that have confounded TB control. There will be no lasting reduction of TB morbidity and mortality without rapid and cost-effective TB diagnostics, efficacious vaccines, and shortened, well-tolerated chemotherapy, which can only be developed on the foundation of understanding the biology of the tubercle bacilli and subsequent host-pathogen interactions. The goal of this proposal is to accelerate TB research through the completion and distribution of 4,000 specialized transducing reagents to make precise null bar-coded deletion (PNBCD) mutants in every gene of M. tuberculosis. We plan to make mutants in virulent Mtb strains and mc27902, an attenuated Mtb strain that can be used under BSL2-containment. We will partner with ATCC (BEI) for distribution of these and distribution