title: Effects of non-iron metalloporphyrins on growth and gene expression of Porphyromonas gingivalis.
abstract: The oral anaerobic bacterium Porphyromonas gingivalis, which is implicated as an important pathogen for chronic periodontitis, requires heme for its growth. Non-iron metalloporphyrins, In-PPIX and Ga-PPIX, were examined for antibacterial effects on P. gingivalis. Both In-PPIX and Ga-PPIX caused retardation of P. gingivalis growth in a dose-dependent fashion. Microarray and qPCR analyses revealed that In-PPIX treatment upregulated the expression of several genes encoding proteins including ClpB and ClpC, which are members of the Clp (caseinolytic protease, Hsp100) family, and aRNR, aRNR-activating protein and thioredoxin reductase, whereas In-PPIX treatment had no effect on the expression of genes encoding proteins involved in heme uptake pathways, Hmu-mediated, Iht-mediated and Tlr-mediated pathways. P. gingivalis ihtA and ihtB mutants were more resistant to In-PPIX than was the wild-type parent, whereas hmuR and tlr mutants did not show such resistance to In-PPIX. The results suggest that In-PPIX is incorporated by the Iht-mediated heme uptake pathway and that it influences protein quality control and nucleotide metabolism and retards growth of P. gingivalis.
authors.affiliation: Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Yukitake
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Keiko
authors.initials: K
authors.lastname: Sato
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohara
authors.forename: Mamiko
authors.initials: M
authors.lastname: Yoshimura
authors.forename: Eiko
authors.initials: E
authors.lastname: Sakai
authors.forename: Koji
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006418:Heme / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008665:Metalloporphyrins / Q000494:pharmacology*; D009154:Mutation; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D008665:Metalloporphyrins; D006418:Heme