The identification of uncultured microbial pathogens.

Clinicians have long been aware of human diseases that are associated with visible but uncultured microorganisms. Without the ability to cultivate these organisms, they have remained unidentified. Environmental microbiologists have also discovered on the basis of recent advances in the field of molecular phylogeny that culture-based methods for detecting microorganisms are biased and insensitive. A culture-independent experimental approach is described for the identification of microbial pathogens. This approach incorporates fundamental aspects of 16S rRNA-based molecular phylogeny as well as nucleic acid amplification technology. From its application to Whipple's disease, one can speculate as to the potential insights a highly sensitive, culture-independent method may provide into the diversity and natural ecology of human microbial pathogens.