title: C. pseudotuberculosis Phop confers virulence and may be targeted by natural compounds.
abstract: The bacterial two-component system (TCS) regulates genes that are crucial for virulence in several pathogens. One of such TCS, the PhoPR system, consisting of a transmembrane sensory histidine kinase protein (PhoR) and an intracellular response regulator protein (PhoP), has been reported to have a major role in mycobacterial pathogenesis. We knocked out the phoP in C. pseudotuberculosis, the causal organism of caseous lymphadenitis (CLA), and using a combination of in vitro and in vivo mouse system, we showed for the first time, that the PhoP of C. pseudotuberculosis plays an important role in the virulence and pathogenicity of this bacterium. Furthermore, we modeled the PhoP of C. pseudotuberculosis and our docking results showed that several natural compounds including Rhein, an anthraquinone from Rheum undulatum, and some drug-like molecules may target PhoP to inhibit the TCS of C. pseudotuberculosis, and therefore may facilitate a remarkable attenuation of bacterial pathogenicity being the CLA. Experiments are currently underway to validate these in silico docking results.
authors.affiliation: PG Program in Bioinformatics, Laboratory of Cellular and Molecular Genetics (LGCM), Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. sandip_sbtbi@yahoo.com sintiaalmeida@gmail.com hassan_chemist@yahoo.com Jamal-syedbabar.jamal@gmail.com afojunior@gmail.com edson.folador@gmail.com vini.abreu@gmail.com fernandadorella@gmail.com vasco@icb.ufmg.br.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Tiwari
authors.forename: Marcília Pinheiro
authors.initials: MP
authors.lastname: da Costa
authors.forename: Sintia
authors.initials: S
authors.lastname: Almeida
authors.forename: Syed Shah
authors.initials: SS
authors.lastname: Hassan
authors.forename: Syed Babar
authors.initials: SB
authors.lastname: Jamal
authors.forename: Alberto
authors.initials: A
authors.lastname: Oliveira
authors.forename: Edson Luiz
authors.initials: EL
authors.lastname: Folador
authors.forename: Flavia
authors.initials: F
authors.lastname: Rocha
authors.forename: Vinícius Augusto Carvalho
authors.initials: VA
authors.lastname: de Abreu
authors.forename: Fernanda
authors.initials: F
authors.lastname: Dorella
authors.forename: Rafael
authors.initials: R
authors.lastname: Hirata
authors.forename: Diana Magalhaes
authors.initials: DM
authors.lastname: de Oliveira
authors.forename: Maria Fátima
authors.initials: MF
authors.lastname: da Silva Teixeira
authors.forename: Artur
authors.initials: A
authors.lastname: Silva
authors.forename: Debmalya
authors.initials: D
authors.lastname: Barh
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D001681:Biological Assay; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D003354:Corynebacterium Infections / Q000235:genetics / Q000276:immunology*; D016925:Corynebacterium pseudotuberculosis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014774:Virulence
chemical_list: D000880:Anthraquinones; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C061279:PhoR protein, Bacteria; C061064:PhoP protein, Bacteria; C020491:rhein