ABSTRACT
The task of detecting a known bacterial pathogen in a known infectious disease can sometimes be challenging even when our knowledge of the pathogen is extensive. For instance, the entire genome of the uncultivated bacterium Treponema pallidum has been sequenced and yet the diagnosis of active syphilis remains dependent on non-specific serological tests (VDRL or RPR) that employ a generic phospholipid (cardiolipin) as antigen. The task of detecting unknown or previously undescribed bacterial pathogens in suspected infectious diseases presents an even greater teclmical and philosophical challenge. What does it mean to search for the unknown? In the context of bacterial infection, it means searching for a bacterial pathogen that is associated with a disease without a priori knowledge of the characteristics of the microbe. The implication is that the microbe is occult and defies detection by conventional methods. Such a search should have the broadest scope and should be based on the detection of highly conserved bacterial features.
