Bill Jacobs Lab


Williams Jacobs William R. Jacobs Jr. , Ph.D.
Professor of Genetics
Professor of Microbiology and Immunology
Howard Hughes Medical Institute Investigator
National Academy of Sciences Member

Location: Room 577, Price Center/Block Research Pavilion
Phone: 718.678.1075


microscope image
Journal of Infectious Diseases
GM-CSF differentiated primary human macrophages produce extracellular traps (picogreen staining in green) in the presence of IFN-gamma at 2 days post-infection of M. tuberculosis (visualized by auramine-rhoamine staining in red) (See Wong and Jacobs, pp 109–19
Tuberculosis, caused by Mycobacterium tuberculosis, causes one in four avoidable deaths in the Third World and kills more adults than malaria, AIDS, and all tropical diseases combined. In recent years, there have been dramatic increases in the numbers of new cases worldwide - one of the consequences of the AIDS epidemic. In addition to these increasing incidences, there has been an emergence of M. tuberculosis strains that are resistant to all seven anti-tuberculosis agents. These alarming trends have caused the World Health Organization to declare tuberculosis a global health emergency, a distinction never accorded another disease. My laboratory has focused its efforts on developing systems to genetically manipulate mycobacteria, particularly M. tuberculosis.

These tools have allowed us to:

  1. develop the luciferase reporter phage assay for rapid assessment of drug susceptibilities,
  2. analyze the genes involved in resistance to tuberculosis drugs such as isoniazid, ethionamide, and etyhambutol, and
  3. to identify specific phenotypic properties associated with a tuberculosis pathogenesis.

Current research efforts are aimed at identifying genes involved in the virulence of M. tuberculosis, identifying novel drug targets, generating rapid and robust phage diagnostics for drug resistant strains of M. tuberculosis, and engineering attenuated mutants of M. tuberculosis and other mycobacteria that can be used as live-cell tuberculosis vaccines.

Recent News

News | Identification of a small molecule with activity against drug-resistant and persistent tuberculosis

A cell-based phenotypic screen for inhibitors of biofilm formation in mycobacteria identified the small molecule TCA1, which has bactericidal activity against both drug-susceptible and -resistant Mycobacterium tuberculosis (Mtb) and sterilizes Mtb in vitro combined with rifampicin or isoniazid. In addition, TCA1 has bactericidal activity against nonreplicating Mtb in vitro and is efficacious in acute and chronic Mtb infection mouse models both alone and combined with rifampicin or isoniazid. Transcriptional analysis revealed that TCA1 down-regulates genes known to be involved in Mtb persistence. Genetic and affinity-based methods identified decaprenylphosphoryl- ß-D-ribofuranose oxidoreductase DprE1 and MoeW, enzymes involved in cell wall and molybdenum cofactor biosynthesis, respectively, as targets responsible for the activity of TCA1. These in vitro and in vivo results indicate that this compound functions by a unique mechanism and suggest that TCA1 may lead to the development of a class of antituberculosis agents.


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