title: In silico characterization  of three two-component systems of Ehrlichia canis and evaluation of a  natural plant-derived inhibitor.
abstract: Two-component  signal transduction systems (TCS) are important elements in the interaction of  endobacteria with host cells. They are basically composed of two proteins, an  environmental signal sensor and a response regulator, which activate genes  involved in a wide range of bacterial responses to their environment. We  analyzed three sets of genes corresponding to TCS of Ehrlichia canis, a  common tick-borne canine pathogen and the etiologic agent of canine monocytic  ehrlichiosis, in order to identify the characteristic domains of the sensor and  response regulator components. Analysis of sequence alignments of the  corresponding proteins indicated a high degree of similarity to other members  of the Anaplasmataceae TCS proteins, demonstrating that they could be useful as  universal targets for development of new drugs against these bacteria. We also  evaluated by quantitative PCR inhibition of E. canis by (2H)-1,4-benzoxazin-3(4H)-one  (BOA), the core compound of the plant phenolic compound DIMBOA, which shows  inhibitory action against TCS of the phytopathogen Agrobacterium  tumefasciens. This bacterium exerts its pathogenicity by transferring  oncogenic DNA (T-DNA) into plant cells; this transfer is mediated through a  type-IV secretion system, which is regulated by the VirA/VirG TCS. The process  of infection and pathogenesis of E. canis is associated with the  secretion of effector proteins into the host cell cytoplasm through a T4SS  system, which blocks the cell defense response. We suggest that BOA, and  possibly other plant phenolic compounds that are TCS inhibitors, can be  exploited in the search for new antiehrlichial drugs to be used alone or as  complements in the treatment of canine monocytic ehrlichiosis.
authors.affiliation: Unidade de Biotecnologia, Universidade de Ribeirão Preto, Ribeirão Preto, SP, Brasil.
authors.forename: E V
authors.initials: EV
authors.lastname: Santos
authors.forename: G
authors.initials: G
authors.lastname: Silva
authors.forename: G P
authors.initials: GP
authors.lastname: Cardozo
authors.forename: T A
authors.initials: TA
authors.lastname: Bitencourt
authors.forename: S C
authors.initials: SC
authors.lastname: França
authors.forename: A L
authors.initials: AL
authors.lastname: Fachin
authors.forename: M
authors.initials: M
authors.lastname: Marins
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D048588:Benzoxazines / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D019295:Computational Biology / Q000379:methods*; D041061:Ehrlichia canis / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010944:Plants / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D048588:Benzoxazines; D001688:Biological Products