Identification ofMycobacterium tuberculosisCounterimmune (cim) Mutants in Immunodeficient Mice by Differential Screening

• DOI: 10.1128/iai.72.9.5315-5321.2004
• Publication Date: 2004-08-21T03:12:22Z
• Authors: Katherine B. Hisert; Meghan A. Kirksey; James E. Gomez; Alexandra O. Sousa; Jeffery S. Cox; William R. Jacobs; Carl F. Nathan; John D. McKinney
• Keywords: Identification

Tuberculosis (TB) is characterized by lifetime persistence of Mycobacterium tuberculosis. Despite the induction a vigorous host immune response that curtails disease progression in majority cases, organism not eliminated. Subsequent immunosuppression can lead to reactivation after prolonged period clinical latency. Thus, while it clear protective mechanisms are engaged during M. tuberculosis infection, also appears pathogen has evolved effective countermechanisms. Genetic studies with animal infection models and patients have revealed key role for cytokine gamma interferon (IFN-gamma) resistance TB. IFN-gamma activates large number antimicrobial pathways. Three these IFN-gamma-dependent been implicated defense against tuberculosis: inducible nitric oxide synthase (iNOS), phagosome oxidase (phox), phagosome-associated GTPase LRG-47. In order identify bacterial genes provide protection specific pathways, we developed strategy differential signature-tagged transposon mutagenesis. Using this approach identified three essential progressive growth rapid lethality iNOS-deficient mice but IFN-gamma-deficient mice. We propose involved pathways allow counter other than iNOS.