Suman Laal, PhD

M. tuberculosis is a versatile organism, capable of adapting to a variety of different environments. We have provided evidence that M. tuberculosis alters the profile of antigenic proteins expressed in vivo during different stages of disease progression. Understanding of the host-pathogen interactions and the immune events that occur during the early stages post-infection is required for obtaining insight into the pathogenesis of M. tuberculosis infection, and for design of rational intervention strategies for TB. The current interests of our laboratory are two fold. First, to understand the M. tuberculosis-host interaction that occurs during the early stages post-infection, we have conducted studies with animal models of TB, and identified several novel proteins of M. tuberculosis that are expressed in vivo by the inhaled bacteria during the first few weeks post-infection. Many of these proteins have characteristics of surface or secreted proteins, and have structural similarities to proteins involved in binding/adhesion/invasion in other bacteria. Studies aimed at defining the role of these proteins in interaction with the host cells, and in eliciting cellular and humoral immune responses are ongoing. These studies will provide insight into the host-pathogen interaction that occurs upon infection. In addition, these proteins could be candidates for devising vaccines, and/or surrogate markers for identifying individuals with active, pre-clinical infection with M. tuberculosis.

Second, based on a systematic analysis of the humoral immune responses of TB patients at different stages of disease progression, we have identified a set of immuno-dominant culture filtrate proteins of M. tuberculosis that are candidates for devising a rapid, point-of-care diagnostic test for TB. Some of these candidate proteins have been cloned and are currently being dissected to identify the immuno-dominant epitopes associated with active disease. We have also provided evidence that anti-mycobacterial antibodies are present in the urine of TB patients. In view of the lack of resources and infrastructure in developing countries, the high prevalence of active and latent TB in these countries, the increasing incidence of HIV-infection, and the high rates of reactivation TB in the co-infected patients, these studies raise the exciting possibility of developing an inexpensive, safe, urine-based immuno-diagnostic test for TB. Efforts to devise such a test are also ongoing.