Genetic requirements for mycobacterial survival during infection

By Christopher M. Sassetti, Eric J. Rubin. Proceedings of the National Academy of Sciences of the United States of America, 2003

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Despite the importance of tuberculosis as a public health problem, we know relatively little about the molecular mechanisms used by the causative organism, Mycobacterium tuberculosis, to persist in the host. To define these mechanisms, we have mutated virtually every nonessential gene of M. tuberculosis and determined the effect disrupting each gene on the growth rate of this pathogen during infection. A total of 194 genes that are specifically required for mycobacterial growth in vivo were identified. The behavior of these mutants provides a detailed view of the changing environment that the bacterium encounters as infection proceeds. A surprisingly large fraction of these genes are unique to mycobacteria and closely related species, indicating that many of the strategies used by this unusual group of organisms are fundamentally different from other pathogens.

Subfields: Epidemiology, Infectious Diseases, Surgery

View Paper: https://www.semanticscholar.org/paper/5e5aa78b3027d3623c7395cae12a2a0bb9600273

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Citations in the corpus

Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved (2010, neutral): “The 'essential' gene category was defined on the basis of genome-wide analyses of transposon insertion mutants that were unable to grow on Middlebrook 7H11 agar or in the spleens of intravenously infected mice, as reported previousl”
Mycobacterial persistence requires the utilization of host cholesterol (2008, background): “In contrast, mutations in the mce4 operon have little effect for the first 2 weeks of infection and only attenuate bacterial growth in this organ after the onset of adaptive immunity (20, 21).”
Pathway to Synthesis and Processing of Mycolic Acids in Mycobacterium tuberculosis (2005, neutral): “tuberculosis in mouse lung macrophages (88).”
Mycobacterium tuberculosis: Success through dormancy (2012, background): “Several other mycobacterial genes have been implicated in ROS and RNS detoxification (indepth reviewed by Ehrt & Schnappinger, 2009): • sodA and sodC, both encoding a superoxide dismutase (Dussurget et al., 2001; Edwards et al., 2001; Pidding- ton et al., 2001; Sassetti & Rubin, 2003).”
The spectrum of latent tuberculosis: rethinking the goals of prophylaxis (2009, neutral): “Genome-wide mutagenesis studies have been instrumental in elucidating the essential nature of genes that are required for initial growth in the mouse mode”
High-Resolution Phenotypic Profiling Defines Genes Essential for Mycobacterial Growth and Cholesterol Catabolism (2011, methodology): “When we compared these data to previous genome-wide screens for mutants attenuated in mouse models of infection [46] we found that a full ten percent of genes specifically required for bacterial growth in vivo are also required for the utilization of cholesterol in vitro (Table S3).”
Targeting virulence: a new paradigm for antimicrobial therapy (2007, background): “tuberculosis genome, were required for in vivo survival than were required for in vitro growt”