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This Week in TB R&D – 8 June 2010


7 Jun 2010
by Working Group

Science Textbook
The TB Pipeline starts here!

Our goal is to keep our audience up to date on the latest TB drug research & development. The past couple of months have seen a flurry of publishing activity. In order to present these to you quickly, we are diverging from our usual one-by-one analysis in favor of brief synopses with links to the abstracts or full paper for a few of these interesting papers.

Specific drug related papers:

  1. Two recent papers on PA-824 where published in Antimicrobial Agents and Chemotherapy. The first paper investigates an alternate drug delivery strategy for PA-824 and the second shares PA-824 Phase II clinical trial data. They are ‘Dry Powder PA-824 Aerosols for Treatment of Tuberculosis in Guinea Pigs’ by Lucila Garcia-Contreras and colleagues and ‘Early Bactericidal Activity and Pharmacokinetics of PA-824 in Smear-Positive Tuberculosis Patients (AAC01354-09)’ by Andreas Diacon and colleagues.
  2. PLoS ONE published two papers on two different drugs- Thioridazine and Thiolactomycin, respectively. ‘A Mycobacterium tuberculosis Sigma Factor Network Responds to Cell-Envelope Damage by the Promising Anti-Mycobacterial Thioridazine’ by Noton Dutta, Smriti Mehra and Deepak Kaushal; and ‘Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH’ by Qosay Al-Balas and colleagues.

Science released a couple brief reviews on TB in their recent ‘Special Section’ dedicated to TB and Malaria:

  1. Tuberculosis: What We Don’t Know Can, and Does, Hurt Us’ by David Russell, Clifton Barry 3rd, and Joanne Flynn. A brief overview of the pressing need develop new vaccines, drugs, and diagnostics coupled with the importance of identifying biomarkers and supporting failing health-care systems.
  2. The Population Dynamics and control of Tuberculosis’ by Christopher Dye and Brian Williams. A concise evaluation of the epidemiology of TB in light of current social and scientific developments.

A few articles related to M. tb survival and metabolism mechanisms in the host:

  1. In PNAS, ‘Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection’ by Joeli Marrero, Kyu Rhee, Dirk Schnappinger, Kevin Pethe, and Sabine Ehrt.
  2. In J of Bacteriology, ‘Revisiting the assignment of Rv0241c enzyme to the Fatty Acid Synthase type II of Mycobacterium tuberculosis’ by Emmanuelle Sacco and colleagues.
  3. In PloS, ‘Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen’ by Shilpi Jayaswal and colleagues. In a March post, we commented on work from this lab which used a whole genome based siRNA approach to identify host factors which allow bacterial survival. This article delves deeper to identify proteins of the host signaling system which permit bacterial survival by knocking down host kinases and phosphatases in H37Rv infected murine macrophages.

Finally, the New England Journal of Medicine published a paper by Khor and colleagues which suggested single-nucleotide polymorphisms (SNPs) in the cytokine-inducible SRC homology 2 (SH2) domain protein (CISH) gene may convey an ~18% increased risk of infection to various infectious diseases including TB.

Your comments and thoughts about these papers, others you have read and what impact they add to the field are welcomed!

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