November 2011

Targeting tuberculosis

Talks to cover what we know about molecular details of host-pathogen relationship and how the bacterium is affected by our attempts to stop its spread  

Meetings_TBTuberculosis kills between 2 million and 3 million people each year and continues to be a major global health concern. Mycobacterium tuberculosis, the etiologic agent responsible, is an obligate human pathogen that has infected mankind since the dawn of time. The emergence of highly drug-resistant forms of the disease threatens to completely undermine disease-control efforts and even may be shifting the fundamental pathobiology of the host-pathogen relationship.

The community of scientists engaged in studying this deadly disease has made dramatic advances in understanding the biology and biochemistry of this deadly pathogen, but many important details are only now starting to be appreciated. These three symposia in the tuberculosis theme will bring together diverse speakers struggling to understand the molecular details of the host-pathogen relationship and how the bacterium may be adapting to human attempts to bring the disease under control. The subjects were chosen so that the three symposia build upon each other by providing state-of-the-art lectures covering our understanding of the in vivo biochemistry, how it drives the host-pathogen relationship and how this relationship may be changing as new strains of the bacterium adjust.

In vivo biochemistry of the pathogen 

The first session, chaired by Squire J. Booker (The State University of Pennsylvania), will provide an overview of the adaptations that M. tuberculosis makes to survive in the challenging environment of the human lung. The bacterium faces many obstacles to replication in the face of the human immune response, obstacles that have driven unusual and distinct biochemical adaptations.

A lecture by Valerie Mizrahi (University of Cape Town), titled “Mechanisms of DNA Repair and Mutagenesis in M. Tuberculosis,” will describe her laboratory’s contributions to the understanding of the complex systems of DNA repair that have evolved in response to the need to maintain the integrity of this molecule in the face of both the organism’s exceedingly long generation time and the continuous oxidative and nitrosative stress challenges mounted by the host immune system.

William R. Jacobs (Albert Einstein College of Medicine) will describe his lab’s efforts to understand the biochemical details of cell-envelope construction – essential for understanding the mechanism of antitubercular drugs and in the construction of new vaccines. Jacobs’ group made a particularly important contribution to understanding transport of one of the most important of the disaccharides used in cell wall biogenesis, trehalose.

Natasha Nesbitt (State University of New York, Stony Brook) will present a lecture titled “Cholesterol Metabolism in Mycobacterium Tuberculosis: Chewing through the Fat.” She will describe her work with Nicole Sampson on cholesterol utilization in M. tuberculosis, which is important because, in the intracellular environment of the host, M. tuberculosis shifts from a carbohydrate-based metabolism to a lipid-based metabolism. Moreover, it can utilize cholesterol as its sole carbon source in culture.

Biochemical mediators of the host-pathogen interaction 

The second session, chaired by Clifton E. Barry III (National Institutes of Health), will feature a lecture from Carolyn Bertozzi (University of California at Berkeley) titled “Chemical Approaches for Probing Mycobacterial Metabolites.” Bertozzi will describe her lab’s chemistry-driven approach to understanding microbial metabolism and adaptation of that metabolism to the host environment.

Sonia Flores (University of Colorado Denver) will give a talk titled “Vitamin D-Dependent Innate Antibacterial Responses on Tuberculous and Non-tuberculous Mycobacteria.”

The session will end with a lecture from Mary Jackson (Colorado State University-Fort Collins) titled “Biogenesis of Mycobacterial Cell Envelope Glycoconjugates,” in which she will elaborate on her lab’s longstanding interest in the biogenesis of one class of the most important mediators of the host-pathogen relationship.

Relationship of host and pathogen 

The final session will be chaired by Jackson and will feature a lecture from Barry. In “Molecular Mechanisms of the Evolution of Drug Resistance in TB,” Barry will describe his lab’s attempts to understand the molecular evolution of resistance and subsequent fitness adaptations in highly drug-resistant clinical isolates.

Miriam Braunstein (University of North Carolina at Chapel Hill School of Medicine) will deliver a lecture titled “Protein Export via the Accessory Sec System of Mycobacterium tuberculosis.” She will describe her lab’s elaboration of the mechanisms of protein secretion developed by M. tuberculosis to enable survival in the macrophage phagosome.

Finally, Sarah Fortune (Harvard School of Public Health) will deliver a lecture titled “On the Clock: Diversity through Growth and Division in Mycobacteria,” describing her lab’s attempts to probe adaptation of extant strains of M. tuberculosis using next-generation sequencing approaches to identify and understand polymorphisms that are geographically or pathogenically unique.

The three symposia also will include presentations chosen from submitted abstracts and will be complemented by related poster sessions. These symposia will present a unique opportunity for investigators interested in the biochemistry and detailed molecular mechanisms underlying the pathogenesis of this important disease to be exposed to an exciting selection of some of the most important recent developments in this area. 


Squire J. Booker ( is an associate professor of chemistry and associate professor of biochemistry and molecular biology at The Pennsylvania State University.  Clifton E. Barry III ( is a senior investigator and chief of the tuberculosis research section at the National Institute of Allergy and Infectious Diseases.  

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