# Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure
## 5 Protein Synthesis, Export and Filament Elongation
### Genetic Regulation of FliC and FliD
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \multirow{2}{*}{**Protein**} & \multirow{2}{*}{**Function**} & \multirow{2}{*}{**Sigma Factor**} & \multicolumn{2}{c}{**Class in Flagellar Regulatory**} & \multirow{2}{*}{**Transcriptional Expression Regulators**} & \multirow{2}{*}{**Post- Transcriptional Segection**} \\  & & & & **3-Tiered** & & & **4-Tiered** \\ \hline \multirow{4}{*}{Flagellin (FliC, FlaA)} & Structural component of the filament & Sigma28 Sigma43 & \multirow{4}{*}{Class III gene} & \multirow{4}{*}{Class IV gene} & \multicolumn{2}{c}{ConJY Environmental factors (nutrients, c-di-GMP, pCp, BCA,...)} & \multirow{4}{*}{FliS} \\  & & Sigma28 Sigma43 & & & & & \\ \cline{1-1}  & & Sigma70 & & & & & \\ \cline{1-1}  & & Sigma28 Sigma43 & & & & & \\ \cline{1-1}  & & Sigma70 & & & & & \\ \cline{1-1}  & & Sigma28 Sigma54 & & & & & \\ \hline \end{tabular}
\end{table} 
Table 1: Flagellins and FliD and their regulators. Figure 4: Genetic organization of main flagellar proteins involved in filament formation. The transcription of flagellar genes is hierarchical and controlled by different promoter classes that are temporally regulated. In peritrichous bacteria, flagellar genes are organized into three classes (I–III) and in monotrichous/polar bacteria the flagellar genes are organized into four classes, both starting with the transcription of the class I master regulator (MR*). Red arrows indicate the proteins and/or transcription factors responsible for the transcription activation of each corresponding class of flagellar genes. Black narrow arrows indicate positive activation/induction and black arrows with a vertical line tip (1) indicate inhibition. Genes involved in filament synthesis and their cognate chaperones are represented in italic colored font. Recently, [PERSON] et al. found that flagellar gene expression in _Salmonella_ is bimodal, meaning that in a population of genetically identical cells under the same conditions only a fraction of them is motile [106; 107]. This bimodality is present at both the class II and class III levels and is governed by separate mechanisms. While a double negative feedback loop involving two flagellar regulatory proteins, RfIP and FliZ, controls the expression of the class II genes in response to nutrient availability, class III gene expression is tuned by the secretion of FlgM and there is a minimum number of HBBs necessary for the cell to pass this checkpoint. In bacteria with a polar flagellum, flagellar genes are transcribed in a four-tiered hierarchy, with genes encoding components of the HBB split between class II and class III (Figure 4) [101]. Gene regulation in _Pseudomonas_ is more complex and involves the activation of the two-component system FleS-FleR and another sigma factor RepoN (\(\sigma^{54}\)) to activate class III genes. In addition, unlike in _Salmonella_, FliA (\(\sigma^{28}\)) is constitutively expressed in _Pseudomonas_ independently of other flagellar genes, which makes it one of the class I genes [101]. In bacteria with multiple flagellins, such as _Helicobacter_ and _Campylobacter_, expression is under the control of different sigma factors with FlaA under control of \(\sigma^{28}\), while FlaB is under control of \(\sigma^{54}\)[108; 109]. Although the major flagellin is usually under the control of \(\sigma^{28}\), there are exceptions such as _V. cholera_ and _S. oneidensis_ in which the major flagellin is dependent on \(\sigma^{54}\), while commensal gut bacteria of _Eubacterium_ and _Roseburia_ species are under the control of \(\sigma^{28}\) and \(\sigma^{43}\)[110; 111]. In the phylogenetically related _Butyriubrio fibrisolvens_, transcription of one _fliC_ gene is driven from two different promoters, yielding two transcripts with alternative transcription start-sites [111].