1. Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics.

    Lab On a Chip 15(10):2297 (2015) PMID 25882432 PMCID PMC4437799

    Detection of bacteria in bloodstream infections and their antibiotic susceptibility patterns is critical to guide therapeutic decision-making for optimal patient care. Current culture-based assays are too slow (>48 h), leading to excessive up-front use of broad-spectrum antibiotics and/or incorr...
  2. Simultaneous generation of many RNA-seq libraries in a single reaction.

    Nature Methods 12(4):323 (2015) PMID 25730492

    Although RNA-seq is a powerful tool, the considerable time and cost associated with library construction has limited its utilization for various applications. RNAtag-Seq, an approach to generate multiple RNA-seq libraries in a single reaction, lowers time and cost per sample, and it produces dat...
  3. Mechanisms of β-lactam killing and resistance in the context of Mycobacterium tuberculosis.

    Journal of Antibiotics 67(9):645 (2014) PMID 25052484

    β-Lactams are one of the most useful classes of antibiotics against many common bacterial pathogens. One exception is Mycobacterium tuberculosis. However, with increasing incidence of multidrug-resistant tuberculosis and a need for new agents to treat it, the use of β-lactams, specifically the c...
  4. Mechanisms of β-lactam killing and resistance in the context of Mycobacterium tuberculosis.

    Journal of Antibiotics 67(9):645 (2014) PMID 25052484

    β-Lactams are one of the most useful classes of antibiotics against many common bacterial pathogens. One exception is Mycobacterium tuberculosis. However, with increasing incidence of multidrug-resistant tuberculosis and a need for new agents to treat it, the use of β-lactams, specifically the c...
  5. Bacterial toxins and small molecules elucidate endosomal trafficking

    Trends in Microbiology 22(2):53 (2014)

    Bacterial toxins and small molecules are useful tools for studying eukaryotic cell biology. In a recent issue of PNAS, Gillespie and colleagues describe a novel small molecule inhibitor of bacterial toxins and virus trafficking through the endocytic pathway, 4-bromobenzaldehyde N-(2,6-...
  6. Bacterial toxins and small molecules elucidate endosomal trafficking.

    Trends in Microbiology 22(2):53 (2014) PMID 24370463

    Bacterial toxins and small molecules are useful tools for studying eukaryotic cell biology. In a recent issue of PNAS, Gillespie and colleagues describe a novel small molecule inhibitor of bacterial toxins and virus trafficking through the endocytic pathway, 4-bromobenzaldehyde N-(2,6-dimethylph...
  7. Identification of host-targeted small molecules that restrict intracellular Mycobacterium tuberculosis growth.

    PLoS Pathogens 10(2):e1003946 (2014) PMID 24586159 PMCID PMC3930586

    Mycobacterium tuberculosis remains a significant threat to global health. Macrophages are the host cell for M. tuberculosis infection, and although bacteria are able to replicate intracellularly under certain conditions, it is also clear that macrophages are capable of killing M. tuberculosis if...
  8. Identification of host-targeted small molecules that restrict intracellular Mycobacterium tuberculosis growth.

    PLoS Pathogens 10(2):e1003946 (2014) PMID 24586159 PMCID PMC3930586

    Mycobacterium tuberculosis remains a significant threat to global health. Macrophages are the host cell for M. tuberculosis infection, and although bacteria are able to replicate intracellularly under certain conditions, it is also clear that macrophages are capable of killing M. tuberculosis if...
  9. Synthesis and structure-activity relationships of phenyl-substituted coumarins with anti-tubercular activity that target FadD32.

    Bioorganic & Medicinal Chemistry Letters 23(22):6052 (2013) PMID 24103299

    In an effort to develop new and potent agents for therapy against tuberculosis, a high-throughput screen was performed against Mycobacterium tuberculosis strain H37Rv. Two 6-aryl-5,7-dimethyl-4-phenylcoumarin compounds 1a and 1b were found with modest activity. A series of coumarin derivatives w...
  10. Synthesis and structure–activity relationships of phenyl-substituted coumarins with anti-tubercular activity that target FadD32

    Bioorganic & Medicinal Chemistry Letters 23(22):6052 (2013)

  11. Identification of novel inhibitors of nonreplicating Mycobacterium tuberculosis using a carbon starvation model.

    ACS Chemical Biology 8(10):2224 (2013) PMID 23898841 PMCID PMC3864639

    During Mycobacterium tuberculosis infection, a population of bacteria is thought to exist in a nonreplicating state, refractory to antibiotics, which may contribute to the need for prolonged antibiotic therapy. The identification of inhibitors of the nonreplicating state provides tools that can ...
  12. Identification of novel inhibitors of nonreplicating Mycobacterium tuberculosis using a carbon starvation model.

    ACS Chemical Biology 8(10):2224 (2013) PMID 23898841 PMCID PMC3864639

    During Mycobacterium tuberculosis infection, a population of bacteria is thought to exist in a nonreplicating state, refractory to antibiotics, which may contribute to the need for prolonged antibiotic therapy. The identification of inhibitors of the nonreplicating state provides tools that can ...
  13. Identification of novel inhibitors of nonreplicating Mycobacterium tuberculosis using a carbon starvation model.

    ACS Chemical Biology 8(10):2224 (2013) PMID 23898841 PMCID PMC3864639

    During Mycobacterium tuberculosis infection, a population of bacteria is thought to exist in a nonreplicating state, refractory to antibiotics, which may contribute to the need for prolonged antibiotic therapy. The identification of inhibitors of the nonreplicating state provides tools that can ...
  14. Diarylcoumarins inhibit mycolic acid biosynthesis and kill Mycobacterium tuberculosis by targeting FadD32.

    PNAS 110(28):11565 (2013) PMID 23798446 PMCID PMC3710825

    Infection with the bacterial pathogen Mycobacterium tuberculosis imposes an enormous burden on global public health. New antibiotics are urgently needed to combat the global tuberculosis pandemic; however, the development of new small molecules is hindered by a lack of validated drug targets. He...
  15. Diarylcoumarins inhibit mycolic acid biosynthesis and kill Mycobacterium tuberculosis by targeting FadD32.

    PNAS 110(28):11565 (2013) PMID 23798446 PMCID PMC3710825

    Infection with the bacterial pathogen Mycobacterium tuberculosis imposes an enormous burden on global public health. New antibiotics are urgently needed to combat the global tuberculosis pandemic; however, the development of new small molecules is hindered by a lack of validated drug targets. He...
  16. CCT chaperonin complex is required for efficient delivery of anthrax toxin into the cytosol of host cells.

    PNAS 110(24):9932 (2013) PMID 23716698 PMCID PMC3683768

    Bacterial toxins have evolved successful strategies for coopting host proteins to access the cytosol of host cells. Anthrax lethal factor (LF) enters the cytosol through pores in the endosomal membrane formed by anthrax protective antigen. Although in vitro models using planar lipid bilayers hav...
  17. CCT chaperonin complex is required for efficient delivery of anthrax toxin into the cytosol of host cells.

    PNAS 110(24):9932 (2013) PMID 23716698 PMCID PMC3683768

    Bacterial toxins have evolved successful strategies for coopting host proteins to access the cytosol of host cells. Anthrax lethal factor (LF) enters the cytosol through pores in the endosomal membrane formed by anthrax protective antigen. Although in vitro models using planar lipid bilayers hav...
  18. Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis.

    Nature Chemical Biology 9(6):398 (2013) PMID 23603659

    Formation of the inflammasome, a scaffolding complex that activates caspase-1, is important in numerous diseases. Pyroptotic cell death induced by anthrax lethal toxin (LT) is a model for inflammasome-mediated caspase-1 activation. We discovered 7-desacetoxy-6,7-dehydrogedunin (7DG) in a phenoty...
  19. Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis.

    Nature Chemical Biology 9(6):398 (2013) PMID 23603659

    Formation of the inflammasome, a scaffolding complex that activates caspase-1, is important in numerous diseases. Pyroptotic cell death induced by anthrax lethal toxin (LT) is a model for inflammasome-mediated caspase-1 activation. We discovered 7-desacetoxy-6,7-dehydrogedunin (7DG) in a phenoty...
  20. Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response.

    Virulence 4(4):273 (2013) PMID 23563389 PMCID PMC3710330

    Certain bacterial pathogens are able to evade the host immune system and persist within the human host. The consequences of persistent bacterial infections potentially include increased morbidity and mortality from the infection itself as well as an increased risk of dissemination of disease. Er...