title: Transcriptional analysis of the MrpJ network: modulation of diverse virulence-associated genes and direct regulation of mrp fimbrial and flhDC flagellar operons in Proteus mirabilis.
abstract: The enteric bacterium Proteus mirabilis is associated with a significant number of catheter-associated urinary tract infections (UTIs). Strict regulation of the antagonistic processes of adhesion and motility, mediated by fimbriae and flagella, respectively, is essential for disease progression. Previously, the transcriptional regulator MrpJ, which is encoded by the mrp fimbrial operon, has been shown to repress both swimming and swarming motility. Here we show that MrpJ affects an array of cellular processes beyond adherence and motility. Microarray analysis found that expression of mrpJ mimicking levels observed during UTIs leads to differential expression of 217 genes related to, among other functions, bacterial virulence, type VI secretion, and metabolism. We probed the molecular mechanism of transcriptional regulation by MrpJ using transcriptional reporters and chromatin immunoprecipitation (ChIP). Binding of MrpJ to two virulence-associated target gene promoters, the promoters of the flagellar master regulator flhDC and mrp itself, appears to be affected by the condensation state of the native chromosome, although both targets share a direct MrpJ binding site proximal to the transcriptional start. Furthermore, an mrpJ deletion mutant colonized the bladders of mice at significantly lower levels in a transurethral model of infection. Additionally, we observed that mrpJ is widely conserved in a collection of recent clinical isolates. Altogether, these findings support a role of MrpJ as a global regulator of P. mirabilis virulence.
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, New York, USA.
authors.forename: Nadine J
authors.initials: NJ
authors.lastname: Bode
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, New York, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Debnath
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, New York, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kuan
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, New York, USA.
authors.forename: Anjelique
authors.initials: A
authors.lastname: Schulfer
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, New York, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Ty
authors.affiliation: Department of Microbiology, New York University Medical Center, New York, New York, USA Melanie.Pearson@nyumc.org.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Pearson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002876:Chromosomes, Bacterial; D005407:Flagella / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009876:Operon / Q000235:genetics*; D011513:Proteus mirabilis / Q000378:metabolism* / Q000472:pathogenicity; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014552:Urinary Tract Infections / Q000382:microbiology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C436707:MrpJ protein, Proteus mirabilis; D012097:Repressor Proteins
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