title: Use of the Salmonella MgtR peptide as an antagonist of the Mycobacterium MgtC virulence factor.
abstract: BACKGROUND
  The MgtC virulence factor has been proposed as an attractive target for antivirulence strategies because it is shared by several important bacterial pathogens, including Salmonella enterica and Mycobacterium tuberculosis (Mtb).
  
  
  OBJECTIVE
  A natural antagonistic peptide, MgtR, which interacts with MgtC and modulates its stability, has been identified in Salmonella, and we investigated its efficiency to target MgtC in another pathogen.
  
  
  METHODS
  We evaluated the interaction between Salmonella MgtR peptide and the Mtb MgtC protein using an in vivo bacterial two-hybrid system and we addressed the effect of exogenously added synthetic MgtR and endogenously expressed peptide.
  
  
  RESULTS
  MgtR peptide strongly interacted with Mtb MgtC protein and exogenously added synthetic MgtR peptide-reduced Mtb MgtC level and interfered with the dimerization of Mtb MgtC. Importantly, heterologous expression of MgtR in Mycobacterium bovis BCG resulted in increased phagocytosis and reduced intramacrophage survival.
  
  
  CONCLUSIONS
  MgtR peptide can target Mtb MgtC protein and reduce mycobacterial macrophage resistance, thus providing a promising new scaffold for the development of antivirulence compounds.
authors: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.|CNRS, UMR5235, 34095 Montpellier Cedex 05, France.
authors: Claudine
authors: C
authors: Belon
authors: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.|CNRS, UMR5235, 34095 Montpellier Cedex 05, France.
authors: Mariana
authors: M
authors: Rosas Olvera
authors: Université de Montpellier, Montpellier, F-34090, France.
authors: Eric
authors: E
authors: Vives
authors: INSERM, DIMNP, CNRS-UMR5235, Montpellier, France.|Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS - FRE 3689), 1919 route de Mende, 34293 Montpellier, France.
authors: Laurent
authors: L
authors: Kremer
authors: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.|CNRS, UMR5235, 34095 Montpellier Cedex 05, France.
authors: Laila
authors: L
authors: Gannoun-Zaki
authors: Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université de Montpellier, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.|CNRS, UMR5235, 34095 Montpellier Cedex 05, France.
authors: Anne-Béatrice
authors: AB
authors: Blanc-Potard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009163:Mycobacterium bovis / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D010452:Peptide Biosynthesis; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010587:Phagocytosis; D055503:Protein Multimerization; D012486:Salmonella typhimurium / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D037521:Virulence Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D010455:Peptides; D037521:Virulence Factors
keywords: MgtC; Mycobacterium tuberculosis; antivirulence strategy; macrophage; membrane peptide; protein–protein interactions