We propose to identify and to study the physiological systems of spirochetes that confer selective advantages upon these bacteria in natural environments that contain extremely low levels of growth substrates and/or are viscous. In such environments spirochetes commonly thrive and compete successfully with other microorganisms. The ability to establish themselves in these environments is found in spirochetes that participate in infectious processes, in spirochetes indigenous to healthy humans and animals, and in free-living spirochetes. Various species of host-associated and free-living spirochetes that can be cultured in vitro will be studied. Investigations on physiology and on competitive interactions at very low substrate concentrations will include studies on spirochetes growing together with other bacteria in continuous culture, as well as comparative studies on substrate transport, on cell surface to volume ratios, on levels of dissimilatory enzymes, and on chemotactic responses. Activities on selected metabolic systems and cell growth at elevated viscosities will be studied in experiments comparing spirochetes to other bacteria. The physiological properties that we plan to investigate are likely to be common to all spirochetes, or to be widespread among these bacteria. Thus, findings of the proposed studies not only will increase our knowledge of the biology of spirochetes in general, but will also be applicable to the understanding of the physiology and cultural conditions of those spirochetes that cannot be cultivated in vitro at present, including forms pathogenic for humans (e.g., Treponema pallidum, the causative agent of syphilis).