The thermophilic bacterium Thermus thermopilus most likely represents an evolutionary intermediate between todays Gram-positive and -negative bacteria (16). For sugar transport it relies on ABC transporters but, like archaea, it has not yet acquired the sugar phosphotransferase system (PTS). Yet, a homologue of Mlc - which functions as a transport-controlled regulatory protein in the regulation of the glucose PTS in E. coli - manifests itself in T. thermophilus. We propose to analyse the regulatory network of three ABC transporters in T. thermophilus. In particular, we will isolate their specific regulators as well as try to unravel the role of Mlc as a possible global regulator in their expression. We will study the function of MalK, the common transport ATPase for the three systems, by analyzing its potential function in controlling and selecting transport activity. Our working hypothesis is that in the absence of catabolite repression the selection of the carbon source utilized is mediated by controlling ABC transporter activity. We will isolate mutations in genes exbB and exbD and analyze their effect on the activity of the three ABC transporters.