Three million people die each year from tuberculosis (TB) in spite of the use of the existing anti-mycobacterial antibiotics and the BCG vaccine. Clearly, a better vaccine and better ways to treat TB are needed. The purpose of this STTR Phase I feasibility study is to evaluate Mycobacterium tuberculosis-binding interactions with several human cell types and pathogen recognition molecules. Pathogens typically gain entry to a host tissue by using cell-to-cell recognition and attachment mechanisms. Conversely, the innate immune system recognizes many common motifs in microbial cell walls. These motifs are present in M. tuberculosis and bacilli-host binding interactions are increasingly being identified for M. tuberculosis. The experimental aim of the proposed study is to functionally evaluate M. tuberculosis binding interactions with human host molecules and cells under shear conditions that more accurately simulate physiological conditions in the lung. By exploring adhesion events we anticipate the discovery of novel molecular targets that could be used to develop better therapies or an improved vaccine. Blocking these targets may prevent infection by abrogating initial attachment by M. tuberculosis to permissive host cells.
