Tuberculosis Research Unit at Rutgers

Rutgers, The State University of New Jersey

Primary Investigator: David Alland, Jerrold Ellner, Padmini Salgame

Until recently, tuberculosis (TB) has been viewed as a disease that progresses over several discrete stages, principally consisting of a period of infection followed by either active TB disease or a latent state with the potential for reactivation. Similarly, mycobacterium tuberculosis (Mtb) has been viewed as a relatively stable bacterium with little genomic diversity, predictable causes of antibiotic resistance, and phenotypic uniformity both during culture and within its infected host. However, recent findings suggest unexpected heterogeneity in TB disease states, host responses, the genotypes and phenotypes of the bacteria, and among the apparently clonal infecting population of Mtb. This team of researchers is examining whether the heterogenous outcomes of TB infections and treatments are determined by the interplay between heterogeneous host-bacteria transcriptional and metabolic programs. Host and bacteria may be pre-programmed phenotypically or genetically to progress from TB infection to TB disease; and to do so rapidly or slowly; and, with or without extensive inflammation and lung damage. Immune tolerance, evasion or subversion may be another result of these interactions, which could lead to worsening disease and adverse treatment outcomes including relapse. Drug tolerance or resistance is another result of these interactions that may have widespread effects on treatment responses. The TBRU will also study the possibility that immune and drug tolerant Mtb share several transcriptional and metabolic programs and also share some of the same vulnerabilities that could provide therapeutic targets.

For more information about the TBRU’s projects, please see the summaries in RePORTER:

Bacterial and Host Heterogeneity in TB latency, persistence and progression (U19AI162598)

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