flhDC

FlhDC is the master regulator of flagellar biosynthesis in many Gram-negative bacteria, notably Escherichia coli and Salmonella enterica. It is a heteromeric transcriptional regulator composed of FlhD and FlhC, which together form the FlhDC complex. The complex acts at the top of the flagellar gene hierarchy to control the expression of downstream genes required for motility.

Mechanism and gene regulation. FlhDC activates transcription of class II flagellar genes by binding to their promoters and facilitating RNA polymerase recruitment. Class II genes encode components of the flagellar basal body and hook, as well as components of the flagellar export apparatus. The activity of FlhDC sets off a transcriptional cascade: class II gene products enable assembly steps that permit the activity of the alternative sigma factor FliA (sigma 28), which in turn activates class III flagellar genes, including flagellin and other late-stage components. The anti-sigma factor FlgM inhibits FliA until the hook–basal body structure is sufficiently assembled, ensuring orderly assembly of the flagellum.

Regulation and control. FlhDC expression and activity are integrated with environmental and cellular signals. Positive inputs include nutrient status and the cellular cAMP-CRP system, linking motility to metabolic conditions. FlhDC is also subject to post-translational regulation. The Lon protease and ClpXP proteolytic systems can modulate FlhD and FlhC levels, affecting complex activity. In some bacteria, accessory regulators such as YdiV can inhibit FlhDC by preventing DNA binding, providing another layer of control over motility.

Significance. FlhDC is essential for flagellum formation and bacterial motility, influencing behaviors such as chemotaxis, surface attachment, and, in some pathogens, virulence. Mutations in flhDC typically result in loss of motility due to failure to assemble functional flagella.