title: The EAL-like protein STM1697 regulates virulence phenotypes, motility and biofilm formation in Salmonella typhimurium.
abstract: The ubiquitous second messenger c-di-GMP regulates the switching of bacterial lifestyles from motility to sessility and acute to chronic virulence to adjust bacterial fitness to altered environmental conditions. Conventionally, EAL proteins being c-di-GMP phosphodiesterases promote motility and acute virulence phenotypes such as invasion into epithelial cells and inhibit biofilm formation. We report here that in contradiction, the EAL-like protein STM1697 of Salmonella typhimurium suppresses motility, invasion into HT-29 epithelial cell line and secretion of the type three secretion system 1 effector protein SipA, whereas it promotes rdar biofilm formation and CsgD expression. STM1697 can, however, functionally replace the EAL-like protein STM1344 and vice versa, whereby both proteins neither degrade nor bind c-di-GMP. Like STM1344, STM1697 suppresses the transcription of class 2 and class 3 flagella regulon genes by binding to FlhD, a component of the master regulator of the flagella regulon FlhD4 C2 and act additively under numerous conditions. Interestingly, the interaction interface of STM1697 with FlhD2 is distinct from its paralogue STM1344. We predict that the stand alone EAL domain proteins STM1697 and STM1344 belong to a subclass of EAL domain proteins in S. typhimurium, which are all involved in motility, biofilm and virulence regulation through interaction with proteins that regulate flagella function.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177, Stockholm, Sweden.
authors.forename: Irfan
authors.initials: I
authors.lastname: Ahmad
authors.forename: Edvard
authors.initials: E
authors.lastname: Wigren
authors.forename: Soazig
authors.initials: S
authors.lastname: Le Guyon
authors.forename: Santtu
authors.initials: S
authors.lastname: Vekkeli
authors.forename: Andrea
authors.initials: A
authors.lastname: Blanka
authors.forename: Youssef
authors.initials: Y
authors.lastname: El Mouali
authors.forename: Naeem
authors.initials: N
authors.lastname: Anwar
authors.forename: Mary Lay
authors.initials: ML
authors.lastname: Chuah
authors.forename: Heinrich
authors.initials: H
authors.lastname: Lünsdorf
authors.forename: Ronald
authors.initials: R
authors.lastname: Frank
authors.forename: Mikael
authors.initials: M
authors.lastname: Rhen
authors.forename: Zhao-Xun
authors.initials: ZX
authors.lastname: Liang
authors.forename: Ylva
authors.initials: Y
authors.lastname: Lindqvist
authors.forename: Ute
authors.initials: U
authors.lastname: Römling
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D005407:Flagella / Q000235:genetics / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D019073:HT29 Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009068:Movement; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011487:Protein Conformation; D012480:Salmonella Infections; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D008840:Microfilament Proteins; C118287:SipA protein, Salmonella; D010727:Phosphoric Diester Hydrolases