Gene Regulation, Transcriptomics and Proteomics
Jon T. Skare, James A. Carroll, X. Frank Yang, D. Scott Samuels and Darrin R. Akins
from: Borrelia: Molecular Biology, Host Interaction and Pathogenesis (Edited by: D. Scott Samuels and Justin D. Radolf). Caister Academic Press, U.K. (2010)
Lyme disease is a tick-borne infection that can lead to chronic, debilitating complications if not recognized or treated appropriately. Borrelia burgdorferi, the agent of Lyme disease, is maintained in nature by a complex enzootic cycle involving ticks and various vertebrate hosts. Since the initial finding over a decade ago that outer surface lipoproteins OspA and OspC are differentially expressed in the tick and mammal, many studies have reported that B. burgdorferi differentially expresses a vast array of genes and proteins to help it adapt to growth in the unfed tick, feeding tick and mammalian host environments. Several global microarray studies have utilized various cultivation systems to identify genes regulated by environmental cues and/or mammalian host factors. The combined studies have been directed at identifying genes that are differentially expressed during the unique enzootic life cycle of this pathogen. While the microarray studies have identified hundreds of genes that are differentially expressed under various environmental conditions, recent advances in genetic methodologies have begun providing insight into the mechanisms underlying the differential gene expression observed. Although how most genes are transcriptionally regulated in the tick and/or mammal is still unclear, several regulatory proteins, including alternative sigma factors, DNA-binding proteins and transcriptional activators/repressors have been identified that either directly or indirectly control the differential expression of many genes in B. burgdorferi. Studies on the various transcriptional regulators, alternative sigma factors and DNA-binding proteins identified thus far have provided important insights into the adaptive strategies employed by B. burgdorferi as it cycles between the tick and the mammal. In recent years, functional proteomic-based assays also have become an important tool for examining the complement of proteins synthesized by Lyme disease spirochetes under experimental conditions that mimic various host environments read more ...