coli. Loss of both Hha and YdgT was required to dramatically de-repress α-haemolysin production which correlated with the ability of YdgT to attenuate the hha mutant phenotype . Similarly, Hha and YdgT may be able to compensate for any effect on flagellar biosynthesis in the
RO4929097 solubility dmso single deletion mutants making it difficult to discern their individual roles in flagellar biosynthesis regulation. PefI-SrgD were recently identified as negative regulators of flagellar SGC-CBP30 purchase gene expression as they inhibit class I activation at the top of the flagellar biosynthesis transcriptional hierarchy . PefI-SrgD is located within the pef fimbrial operon on the Salmonella virulence plasmid and PefI acts to regulate pef fimbriae expression [25, 26]. Pef fimbriae are involved in bacterial adherence and fluid accumulation in the murine small intestine .
Phylogenetic data indicates that S. Typhimurium acquired pef as part of the serovar-specific virulence plasmid  which carries variable genetic elements required for virulence, fimbriae synthesis, plasmid transmission, innate immune resistance and antibiotic resistance [29, 30]. The dual regulatory action of PefI-SrgD on both pef and flagellar promoters is similar to that seen for the see more regulation of fimbriae and flagella in other pathogens. PapX in uropathogenic E. coli acts to reciprocally regulate the expression of type 1 fimbriae and flagella during urinary tract infection . MrpJ in Proteus mirabilis, an opportunistic urinary tract pathogen, activates MR/P fimbrial production while simultaneously repressing flagellar expression . FimZ in S. Typhimurium coordinates reciprocal expression of type 1 fimbriae and flagella .
The existence of regulatory proteins able to dually control fimbriae and flagella production thus appears as an important evolutionary mechanism allowing tight modulation of adherence or motility phenotypes. Although deletion of pefI-srgD in hha ydgT mutants de-represses the motility defect by re-establishing expression of surface flagella, it does not fully reconstitute class II/III and class III promoter activity to wild type levels suggesting the existence of other negative flagellar regulators. The protease ClpXP has been shown to degrade FlhD4C2 in S. Typhimurium , which may represent another negative mafosfamide regulatory mechanism in hha ydgT mutants. The role of PefI-SrgD in the negative regulation of flagellar biosynthesis exemplifies the evolutionary significance of integrating horizontally acquired regulators into ancestral networks. For example, in S. Typhimurium, the horizontally acquired two-component regulatory system SsrA-SsrB regulates ancestral genes throughout the Salmonella genome [5, 35]. In extraintestinal pathogenic E. coli, the horizontally acquired regulator Hfp interacts with the nucleoid-associated protein H-NS to regulate ancestral genes .