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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2003)

Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually. The unusually low permeability of its cell wall contributes to the ability of M. tuberculosis to grow within host macrophages, a property required for pathogenesis of infection. Mycobacterium marinum is an established model for discovering genes involved in mycobacterial infection. Mycobacterium marinum mutants with transposon insertions in the beta-ketoacyl- acyl carrier protein synthase B gene (kasB) grew poorly in macrophages, although growth in vitro was unaffected. Detailed analyses by thin-layer chromatography, nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, infrared spectroscopy, and chemical degradations showed that the kasB mutants synthesize mycolic acids that are 2 - 4 carbons shorter than wild type; the defect was localized to the proximal portion of the meromycolate chain. In addition, these mutants showed a significant ( similar to 30%) reduction in the abundance of keto-mycolates, with a slight compensatory increase of both alpha- and methoxymycolates. Despite these small changes in mycolate length and composition, the kasB mutants exhibited strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensin and lysozyme. The abnormalities of the kasB mutants were fully complemented by expressing M. tuberculosis kasB, but not by the closely related gene kasA. These studies identify kasB as a novel target for therapeutic intervention in mycobacterial diseases.

    Cover page: Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (1994)
    The final hardware modifications for tritium operation have been completed for the Tokamak Fusion Test Reactor (TFTR) [Fusion Technol. 21, 1324 (1992)]. These activities include preparation of the tritium gas handling system, installation of additional neutron shielding, conversion of the toroidal field coil cooling system from water to a Fluorinert™ system, modification of the vacuum system to handle tritium, preparation, and testing of the neutral beam system for tritium operation and a final deuterium-deuterium (D-D) run to simulate expected deuterium-tritium (D-T) operation. Testing of the tritium system with low concentration tritium has successfully begun. Simulation of trace and high power D-T experiments using D-D have been performed. The physics objectives of D-T operation are production of ≈ 10 MW of fusion power, evaluation of confinement, and heating in deuteriumtritium plasmas, evaluation of α-particle heating of electrons, and collective effects driven by alpha particles and testing of diagnostics for confined a particles. Experimental results and theoretical modeling in support of the D-T experiments are reviewed. © 1994 American Institute of Physics.
      Cover page: Preparations for deuterium–tritium experiments on the Tokamak Fusion Test Reactor*Creative Commons 'BY' version 4.0 license
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