Deciphering bacterial flagellar gene regulatory networks in the genomic era

Synthesis of the bacterial flagellum is a complex process involving dozens of structural and regulatory genes. Assembly of the flagellum is a highly-ordered process, and in most flagellated bacteria the structural genes are expressed in a transcriptional hierarchy that results in the products of these genes being made as they are needed for assembly. Temporal regulation of the flagellar genes is achieved through sophisticated regulatory networks that utilize checkpoints in the flagellar assembly pathway to coordinate expression of flagellar genes. Traditionally, flagellar transcriptional hierarchies are divided into various classes. Class I genes, which are the first genes expressed, encode a master regulator that initiates the transcriptional hierarchy. The master regulator activates transcription a set of structural and regulatory genes referred to as class II genes, which in turn affect expression of subsequent classes of flagellar genes. We review here the literature on the expression and activity of several known master regulators, including FlhDC, CtrA, VisNR, FleQ, FlrA, FlaK, LafK, SwrA, and MogR. We also examine the Department of Energy Joint Genomes Institute database to make predictions about the distribution of these regulators. Many bacteria employ the alternative sigma factors sigma(54) and/or sigma(28) to regulate transcription of later classes of flagellar genes. Transcription by sigma(54)-RNA polymerase holoenzyme requires an activator, and we review the literature on the sigma(54)-dependent activators that control flagellar gene expression in several bacterial systems, as well as make predictions about other systems that may utilize sigma(54) for flagellar gene regulation. Finally, we review the prominent systems that utilize sigma(28) and its antagonist, the anti-sigma(28) factor FlgM, along with some systems that utilize alternative mechanisms for regulating flagellar gene expression.