Regulators of expression of the oligopeptide permease A proteins of Borrelia burgdorferi

Tufts-New England Medical Center, Tufts University School of Medicine, Tupper Research Institute, Division of Geographic Medicine and Infectious Diseases, Boston, MA.; Massachusetts General Hospital, Division of Infectious Diseases, Boston, MA; Hubei University, School of Life Sciences, Wuhan, China; University of Kentucky, Department of Molecular and Cellular Biochemistry and Center for Structural Biology, Lexington, KY

^* To whom correspondence should be addressed. Email: lhu{at}tufts-nemc.org.

	Abstract

Borrelia burgdorferi undergoes an infectious cycle that requires adaptation to different hosts and marked differences in environment. B. burgdorferi copes with its different environments by regulating expression of proteins required for survival in a specific setting. The B. burgdorferi oligopeptide permease (Opp) is one of only a few transporters encoded by in the B. burgdorferi genome. Opp proteins in other bacteria serve multiple environmental adaptation functions. B. burgdorferi appears to broaden the usage of this transporter by utilizing 5 different substrate binding proteins (OppA proteins) that interact with the integral membrane components of the transporter. Expression of the OppA proteins is individually regulated and may play different roles in adaptation to host environments. Very little is known about the mechanisms used by B. burgdorferi to regulate expression of different OppA proteins. Here we show that the alternative sigma factors, RpoS and RpoN, regulate expression of oppA-5 but not other oppA genes. Using a reporter assay in E. coli and gel shift binding assays, we also show that the B. burgdorferi BosR/Fur homologue interacts with the oppA-4 promoter, and another candidate transcription factor, EbfC, interacts with the oppA-5 promoter. Binding to the promoters was confirmed by gel shift assays. Expression of BosR/Fur in its different hosts does appear to parallel expression of oppA-4. A better understanding of the factors involved in gene regulation in B. burgdorferi will help to identify co-regulated proteins that may cooperate to allow the organism to survive in a specific environment.