The ins and outs of Mycobacterium tuberculosis protein export

Mycobacterium tuberculosis is an important pathogen that infects approximately one third of the world’s population and kills almost two million people annually. An important aspect of M. tuberculosis physiology and pathogenesis is its ability to export proteins into and across the thick mycobacterial cell envelope, where they are ideally positioned to interact with the host. In addition to the specific proteins that are exported by M. tuberculosis, the systems through which these proteins are exported represent potential targets for future drug development. M. tuberculosis possesses two well-known and conserved export systems: the housekeeping Sec pathway and the Tat pathway. In addition, M. tuberculosis possesses specialized export systems including the accessory SecA2 pathway and five ESX pathways. Here we review the current understanding of each of these export systems, with a focus on M. tuberculosis, and discuss the contribution of each system to disease and physiology

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap") to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents

Genome Sequence of Azotobacter vinelandii , an Obligate Aerobe Specialized To Support Diverse Anaerobic Metabolic Processes

Azotobacter vinelandii is a soil bacterium related to the Pseudomonas genus that fixes nitrogen under aerobic conditions while simultaneously protecting nitrogenase from oxygen damage. In response to carbon availability, this organism undergoes a simple differentiation process to form cysts that are resistant to drought and other physical and chemical agents. Here we report the complete genome sequence of A. vinelandii DJ, which has a single circular genome of 5,365,318 bp. In order to reconcile an obligate aerobic lifestyle with exquisitely oxygen-sensitive processes, A. vinelandii is specialized in terms of its complement of respiratory proteins. It is able to produce alginate, a polymer that further protects the organism from excess exogenous oxygen, and it has multiple duplications of alginate modification genes, which may alter alginate composition in response to oxygen availability. The genome analysis identified the chromosomal locations of the genes coding for the three known oxygen-sensitive nitrogenases, as well as genes coding for other oxygen-sensitive enzymes, such as carbon monoxide dehydrogenase and formate dehydrogenase. These findings offer new prospects for the wider application of A. vinelandii as a host for the production and characterization of oxygen-sensitive proteins.Fil: Setubal, João C.. Virginia Polytechnic Institute; Estados UnidosFil: Dos Santos, Patricia Carolina. Wake Forest University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; ArgentinaFil: Goldman, Barry S.. Monsanto Company; Estados UnidosFil: Ertesvag, Helga. Norwegian University of Science and Technology; NoruegaFil: Espin, Guadelupe. Universidad Nacional Autónoma de México; MéxicoFil: Rubio, Luis M.. Instituto Imdea Energia; EspañaFil: Valla, Svein. Norwegian University of Science and Technology; NoruegaFil: Almeida, Nalvo F.. Virginia Polytechnic Institute; Estados Unidos. Universidade Federal do Mato Grosso do Sul; BrasilFil: Balasubramanian, Divya. Hiram College; Estados UnidosFil: Cromes, Lindsey. Hiram College; Estados UnidosFil: Curatti, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario; Argentina. Fundación para Investigaciones Biológicas Aplicadas. Centro de Estudios de Biodiversidad y Biotecnología; ArgentinaFil: Du, Zijin. Monsanto Company; Estados UnidosFil: Godsy, Eric. Monsanto Company; Estados UnidosFil: Goodner, Brad. Hiram College; Estados UnidosFil: Hellner Burris, Kaitlyn. Hiram College; Estados UnidosFil: Hernandez, José A.. Midwestern University; Estados UnidosFil: Houmiel, Katherine. Seattle Pacific University; Estados UnidosFil: Imperial, Juan. Centro de Biotecnologia y Genomica de Plantas; EspañaFil: Kennedy, Christina. University of Arizona; Estados UnidosFil: Larson, Timothy J.. Virginia Polytechnic Institute; Estados UnidosFil: Latreille, Phil. Monsanto Company; Estados UnidosFil: Ligon, Lauren S.. Virginia Polytechnic Institute; Estados UnidosFil: Lu, Jing. Monsanto Company; Estados UnidosFil: Mærk, Mali. Norwegian University of Science and Technology; NoruegaFil: Miller, Nancy M.. Monsanto Company; Estados UnidosFil: Norton, Stacie. Monsanto Company; Estados UnidosFil: O'Carroll, Ina P.. Virginia Polytechnic Institute; Estados UnidosFil: Paulsen, Ian. Macquarie University; AustraliaFil: Raulfs, Estella C.. Virginia Polytechnic Institute; Estados UnidosFil: Roemer, Rebecca. Hiram College; Estados Unido