title: A LysR-family transcriptional regulator required for virulence in Brucella abortus is highly conserved among the α-proteobacteria.
abstract: Small RNAs are principal elements of bacterial gene regulation and physiology. Two small RNAs in Brucella abortus, AbcR1 and AbcR2, are required for wild-type virulence. Examination of the abcR loci revealed the presence of a gene encoding a LysR-type transcriptional regulator flanking abcR2 on chromosome 1. Deletion of this lysR gene (bab1_1517) resulted in the complete loss of abcR2 expression while no difference in abcR1 expression was observed. The B. abortus bab1_1517 mutant strain was significantly attenuated in macrophages and mice, and bab1_1517 was subsequently named vtlR for virulence-associated transcriptional LysR-family regulator. Microarray analysis revealed three additional genes encoding small hypothetical proteins also under the control of VtlR. Electrophoretic mobility shift assays demonstrated that VtlR binds directly to the promoter regions of abcR2 and the three hypothetical protein-encoding genes, and DNase I footprint analysis identified the specific nucleotide sequence in these promoters that VtlR binds to and drives gene expression. Strikingly, orthologs of VtlR are encoded in a wide range of host-associated α-proteobacteria, and it is likely that the VtlR genetic system represents a common regulatory circuit critical for host-bacterium interactions.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24060, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Sheehan
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24060, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Budnick
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Catlyn
authors.initials: C
authors.lastname: Blanchard
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dunman
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24060, USA.
authors.forename: Clayton C
authors.initials: CC
authors.lastname: Caswell
mesh_terms: D020561:Alphaproteobacteria / Q000235:genetics*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002003:Brucella abortus / Q000235:genetics* / Q000472:pathogenicity; D017124:Conserved Sequence / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D046228:Microarray Analysis; D011401:Promoter Regions, Genetic; D058727:RNA, Small Untranslated / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D058727:RNA, Small Untranslated; D014157:Transcription Factors; C073470:LysR protein, Bacteria