title: Fur homolog regulates Porphyromonas gingivalis virulence under low-iron/heme conditions through a complex regulatory network.
abstract: Porphyromonas gingivalis is a key pathogen responsible for initiation and progression of chronic periodontitis. Little is known about the regulatory mechanisms of iron and heme uptake that allow P. gingivalis to express virulence factors and survive in the hostile environment of the oral cavity, so we initiated characterization of a P. gingivalis Fur homolog (PgFur). Many Fur paralogs found in microbial genomes, including Bacteroidetes, confirm that Fur proteins have a tendency to be subjected to a sub- or even neofunctionalization process. PgFur revealed extremely high sequence divergence, which could be associated with its functional dissimilarity in comparison with other Fur homologs. A fur mutant strain constructed by insertional inactivation exhibited retarded growth during the early growth phase and a significantly lower tendency to form a homotypic biofilm on abiotic surfaces. The mutant also showed significantly weaker adherence and invasion to epithelial cells and macrophages. Transcripts of many differentially regulated genes identified in the fur mutant strain were annotated as hypothetical proteins, suggesting that PgFur can play a novel role in the regulation of gene expression. Inactivation of the fur gene resulted in decreased hmuY gene expression, increased expression of other hmu components and changes in the expression of genes encoding hemagglutinins and proteases (mainly gingipains), HtrA, some extracytoplasmic sigma factors and two-component systems. Our data suggest that PgFur can influence in vivo growth and virulence, at least in part by affecting iron/heme acquisition, allowing efficient infection through a complex regulatory network.
authors.affiliation: Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Ciuraszkiewicz
authors.forename: M
authors.initials: M
authors.lastname: Smiga
authors.forename: P
authors.initials: P
authors.lastname: Mackiewicz
authors.forename: A
authors.initials: A
authors.lastname: Gmiterek
authors.forename: M
authors.initials: M
authors.lastname: Bielecki
authors.forename: M
authors.initials: M
authors.lastname: Olczak
authors.forename: T
authors.initials: T
authors.lastname: Olczak
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D018441:Biofilms / Q000254:growth & development; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins / Q000235:genetics; D006418:Heme / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology; D046228:Microarray Analysis; D016254:Mutagenesis, Insertional; D010802:Phylogeny; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D012808:Sigma Factor / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D012808:Sigma Factor; D006418:Heme; D007501:Iron; D003546:Cysteine Endopeptidases
keywords: Fur; HmuY; Porphyromonas gingivalis; gingipain; hemagglutinin; periodontitis; phylogeny; virulence