title: MtrR control of a transcriptional regulatory pathway in Neisseria meningitidis that influences expression of a gene (nadA) encoding a vaccine candidate.
abstract: The surface-exposed NadA adhesin produced by a subset of capsular serogroup B strains of Neisseria meningitidis is currently being considered as a vaccine candidate to prevent invasive disease caused by a hypervirulent lineage of meningococci. Levels of NadA are known to be controlled by both transcriptional regulatory factors and a component of human saliva, 4-hydroxyphenylacetic acid. Herein, we confirmed the capacity of a DNA-binding protein termed FarR to negatively control nadA expression. We also found that a known transcriptional regulator of farR in N. gonorrhoeae termed MtrR can have a negative regulatory impact on farR and nadA expression, especially when over-expressed. MtrR-mediated repression of nadA was found to be direct, and its binding to a target DNA sequence containing the nadA promoter influenced formation and/or stability of FarR::nadA complexes. The complexity of the multi-layered regulation of nadA uncovered during this investigation suggests that N. meningitidis modulates NadA adhesin protein levels for the purpose of interacting with host cells yet avoiding antibody directed against surface exposed epitopes.
authors: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors: Jason M
authors: JM
authors: Cloward
authors: William M
authors: WM
authors: Shafer
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000235:genetics*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013045:Species Specificity; D014158:Transcription, Genetic
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; C501982:NadA protein, Neisseria meningitidis; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; D003850:Deoxyribonuclease I