title: The phosphocarrier protein HPr of Neisseria meningitidis interacts with the transcription regulator CrgA and its deletion affects capsule production, cell adhesion, and virulence.
abstract: The bacterial phosphotransferase system (PTS) transports and phosphorylates sugars, but also carries out numerous regulatory functions. The β-proteobacterium Neisseria meningitidis possesses an incomplete PTS unable to transport carbon sources because it lacks a membrane component. Nevertheless, the residual phosphorylation cascade is functional and the meningococcal PTS was therefore expected to carry out regulatory roles. Interestingly, a ΔptsH mutant (lacks the PTS protein HPr) exhibited reduced virulence in mice and after intraperitoneal challenge it was rapidly cleared from the bloodstream of BALB/c mice. The rapid clearance correlates with lower capsular polysaccharide production by the ΔptsH mutant, which is probably also responsible for its increased adhesion to Hec-1-B epithelial cells. In addition, compared to the wild-type strain more apoptotic cells were detected when Hec-1-B cells were infected with the ΔptsH strain. Coimmunoprecipitation revealed an interaction of HPr and P-Ser-HPr with the LysR type transcription regulator CrgA, which among others controls its own expression. Moreover, ptsH deletion caused increased expression of a ΦcrgA-lacZ fusion. Finally, the presence of HPr or phospho-HPr's during electrophoretic mobility shift assays enhanced the affinity of CrgA for its target sites preceding crgA and pilE, but HPr did not promote CrgA binding to the sia and pilC1 promoter regions.
authors: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.|Institut Pasteur, Unité des Infections Bactériennes Invasives, 75000, Paris Cedex, France.
authors: Meriem
authors: M
authors: Derkaoui
authors: Institut Pasteur, Unité des Infections Bactériennes Invasives, 75000, Paris Cedex, France.
authors: Ana
authors: A
authors: Antunes
authors: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Sandrine
authors: S
authors: Poncet
authors: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.|Institut Pasteur, Unité des Infections Bactériennes Invasives, 75000, Paris Cedex, France.
authors: Jamila
authors: J
authors: Nait Abdallah
authors: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Philippe
authors: P
authors: Joyet
authors: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Alain
authors: A
authors: Mazé
authors: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors: Céline
authors: C
authors: Henry
authors: Institut Pasteur, Unité des Infections Bactériennes Invasives, 75000, Paris Cedex, France.
authors: Muhamed-Kheir
authors: MK
authors: Taha
authors: Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.|Centre National de la Recherche Scientifique, UMR8261, Expression Génétique Microbienne, Institut de Biologie Physico-Chimique, 75005, Paris, France.
authors: Josef
authors: J
authors: Deutscher
authors: Institut Pasteur, Unité des Infections Bactériennes Invasives, 75000, Paris Cedex, France.
authors: Ala-Eddine
authors: AE
authors: Deghmane
mesh_terms: D000818:Animals; D017209:Apoptosis; D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C406769:CrgA protein, Neisseria meningitidis; D014157:Transcription Factors; D010770:Phosphotransferases; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr