title: Fur is a repressor of biofilm formation in Yersinia pestis.
abstract: BACKGROUND
  Yersinia pestis synthesizes the attached biofilms in the flea proventriculus, which is important for the transmission of this pathogen by fleas. The hmsHFRS operons is responsible for the synthesis of exopolysaccharide (the major component of biofilm matrix), which is activated by the signaling molecule 3', 5'-cyclic diguanylic acid (c-di-GMP) synthesized by the only two diguanylate cyclases HmsT, and YPO0449 (located in a putative operonYPO0450-0448).
  
  
  RESULTS
  The phenotypic assays indicated that the transcriptional regulator Fur inhibited the Y. pestis biofilm production in vitro and on nematode. Two distinct Fur box-like sequences were predicted within the promoter-proximal region of hmsT, suggesting that hmsT might be a direct Fur target. The subsequent primer extension, LacZ fusion, electrophoretic mobility shift, and DNase I footprinting assays disclosed that Fur specifically bound to the hmsT promoter-proximal region for repressing the hmsT transcription. In contrast, Fur had no regulatory effect on hmsHFRS and YPO0450-0448 at the transcriptional level. The detection of intracellular c-di-GMP levels revealed that Fur inhibited the c-di-GMP production.
  
  
  CONCLUSIONS
  Y. pestis Fur inhibits the c-di-GMP production through directly repressing the transcription of hmsT, and thus it acts as a repressor of biofilm formation. Since the relevant genetic contents for fur, hmsT, hmsHFRS, and YPO0450-0448 are extremely conserved between Y. pestis and typical Y. pseudotuberculosis, the above regulatory mechanisms can be applied to Y. pseudotuberculosis.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Fengjun
authors.initials: F
authors.lastname: Sun
authors.forename: He
authors.initials: H
authors.lastname: Gao
authors.forename: Yiquan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Fang
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tan
authors.forename: Zhaobiao
authors.initials: Z
authors.lastname: Guo
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Xia
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhou
authors.forename: Ruifu
authors.initials: R
authors.lastname: Yang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D018441:Biofilms / Q000254:growth & development*; D001681:Biological Assay; D017173:Caenorhabditis elegans; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015010:Yersinia pestis / Q000235:genetics / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C122178:HMST protein, Yersinia pestis; D012097:Repressor Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP