# Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure
## 6 Filament-Host Interaction
### Secretion of Non-Flagellar Proteins during Host Invasion  
Flagella are commonly recognized as important virulence determinants of bacterial pathogens. The type III protein secretion of the flagellar system may be a general mechanism for the transport of proteins that influence bacterial-host interactions. The flagellar apparatus can secrete several putative virulence proteins, effectors, or toxins, having a wide range of functions, including cytotoxicity, hemolysis, proteolysis and protein phosphorylation/dephosphorylation [185]. Early studies of the pathogenic bacterium _Yersinia enterocolifica_ revealed that its flagellar T3 SS export apparatus promotes secretion of non-effector and non-flagellar extracellular proteins termed Fops [185]. One of the Fops proteins exported by the flagellar secretion system was the virulence-associated phospholipase, YpLA, and its secretion is required for full virulence of _Y. enterocolifica_[185, 186]. Further studies revealed that YpLA was secreted by two endogenous injections T3 SSs in _Y. enterocolifica_ and that filamentless mutants were still competent for YpLA secretion, indicating that filament is not essential for the secretion of this phospholipase [187, 188]. The filament also affects secretion of virulence factors in _Edwardsiella tarda_, a flagellated and virulent Gram-negative bacterium that causes edwardsiellosis in fish. In a _fliC_ in-frame deletion mutant, the diameter of the flagellar filaments is significantly reduced and this mutant shows 100-fold reduced pathogenicity to fish. FliC is required for the protein secretion of the T3 SS and T6 SS in _E. tarda_, since the _fliC_ mutant exhibited a significant diminution or complete absence of three effector proteins secreted though either the T3 SS (EseB and EseC) and or the T6 SS (EvpC) [181]. _C. jejuni_ flagellum has also been implicated as a secretory machine for proteins not required for motility, such as the _Campylobacter_ invasion antigens (Cia proteins). These proteins are required for _C. jejuni_ invasion of human intestinal epithelial cells or survival within these cells [189, 190, 191, 192]. Early studies found that inactivation of the flagellar _flaAlfaB_ locus in _C. jejuni_ strain 81,116 abolished secretion of the Cia proteins [193]. However, a more recent paper showed through a different mutagenesis method that, when the _flaAlfaB_ locus was completely deleted, the mutant strains were still able to secrete the Cia proteins,demonstrating that FlaA and FlaB are not required for secretion of the Cia proteins [194]. Only a minimal flagellar structure that includes the hook and hook-filament junction seems to be required for secretion of the Cias [194]. Thus, the flagellar cap protein FliD and filament proteins FlaA and FlaB are dispensable for Cia protein secretion, while the hook protein FlgE and hook-filament junction proteins FlgK and FlgL are required. These authors suggested that the flagellar T3 SS without a filament could function analogously to an injectisome. In addition, there may be additional proteins that interact with the flagellar hook (i.e., FlgE, FlgK, and/or FlgL) to enable direct delivery of CiaC, that interacts with the tip of the injectisome needle. _C. jejuni_ flagella are involved in the secretion of FlaC, a protein found to increase _C. jejuni_ invasion of Hep-2 epithelial cells [195]. Despite the N- and C-terminal regions of FlaC being highly homologous to flagellins FlaA and FlaB, FlaC lacks the central domain and is not required for the expression of a functional flagellum. At least 18 different Cia proteins have been proposed to be secreted and some of those have been functionally characterized [189; 196; 197; 198; 199; 199]. The process of flagellar biogenesis and polymerization of the flagellar filament is likely to temporally influence the dynamics of secretion of virulence factors in _C. jejuni_. Usually, the secretion of virulence factors in _C. jejuni_ occurs during the hook biogenesis with filament polymerization itself reducing secretion of these factors.