title: Complex regulatory network encompassing the Csr, c-di-GMP and motility systems of Salmonella Typhimurium.
abstract: Bacterial survival depends on the ability to switch between sessile and motile lifestyles in response to changing environmental conditions. In many species, this switch is governed by (3'-5')-cyclic-diguanosine monophosphate (c-di-GMP), a signalling molecule, which is metabolized by proteins containing GGDEF and/or EAL domains. Salmonella Typhimurium contains 20 such proteins. Here, we show that the RNA-binding protein CsrA regulates the expression of eight genes encoding GGDEF, GGDEF-EAL and EAL domain proteins. CsrA bound directly to the mRNA leaders of five of these genes, suggesting that it may regulate these genes post-transcriptionally. The c-di-GMP-specific phosphodiesterase STM3611, which reciprocally controls flagella function and production of biofilm matrix components, was regulated by CsrA binding to the mRNA, but was also indirectly regulated by CsrA through the FlhDC/FliA flagella cascade and STM1344. STM1344 is an unconventional (c-di-GMP-inactive) EAL domain protein, recently identified as a negative regulator of flagella gene expression. Here, we demonstrate that CsrA directly downregulates expression of STM1344, which in turn regulates STM3611 through fliA and thus reciprocally controls motility and biofilm factors. Altogether, our data reveal that the concerted and complex regulation of several genes encoding GGDEF/EAL domain proteins allows CsrA to control the motility-sessility switch in S. Typhimurium at multiple levels.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden. kjonas@mit.edu
authors.forename: Kristina
authors.initials: K
authors.lastname: Jonas
authors.forename: Adrianne N
authors.initials: AN
authors.lastname: Edwards
authors.forename: Irfan
authors.initials: I
authors.lastname: Ahmad
authors.forename: Tony
authors.initials: T
authors.lastname: Romeo
authors.forename: Ute
authors.initials: U
authors.lastname: Römling
authors.forename: Ojar
authors.initials: O
authors.lastname: Melefors
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D018441:Biofilms; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D005407:Flagella / Q000378:metabolism / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D016601:RNA-Binding Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP