title: Involvement of PG2212 zinc finger protein in the regulation of oxidative stress resistance in Porphyromonas gingivalis W83.
abstract: The adaptation of Porphyromonas gingivalis to H2O2-induced stress while inducible is modulated by an unknown OxyR-independent mechanism. Previously, we reported that the PG_2212 gene was highly upregulated in P. gingivalis under conditions of prolonged oxidative stress. Because this gene may have regulatory properties, its function in response to H2O2 was further characterized. PG2212, annotated as a hypothetical protein of unknown function, is a 10.3-kDa protein with a cysteine 2-histidine 2 (Cys2His2) zinc finger domain. The isogenic mutant P. gingivalis FLL366 (ΔPG_2212) showed increased sensitivity to H2O2 and decreased gingipain activity compared to the parent strain. Transcriptome analysis of P. gingivalis FLL366 revealed that approximately 11% of the genome displayed altered expression (130 downregulated genes and 120 upregulated genes) in response to prolonged H2O2-induced stress. The majority of the modulated genes were hypothetical or of unknown function, although some are known to participate in oxidative stress resistance. The promoter region of several of the most highly modulated genes contained conserved motifs. In electrophoretic mobility shift assays, the purified rPG2212 protein did not bind its own promoter region but bound a similar region in several of the genes modulated in the PG_2212-deficient mutant. A metabolome analysis revealed that PG2212 can regulate a number of genes coding for proteins involved in metabolic pathways critical for its survival under the conditions of oxidative stress. Collectively, our data suggest that PG2212 is a transcriptional regulator that plays an important role in oxidative stress resistance and virulence regulation in P. gingivalis.
authors.affiliation: Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, California, USA.
authors.forename: Yuetan
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, California, USA.
authors.forename: Wilson
authors.initials: W
authors.lastname: Aruni
authors.affiliation: School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Tianlong
authors.initials: T
authors.lastname: Luo
authors.affiliation: Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, California, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Roy
authors.affiliation: Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, California, USA Center of Genomics, School of Medicine, Loma Linda University, Loma Linda, California, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, California, USA Institute of Oral Biology, Kyung Hee University, Seoul, Republic of Korea hfletcher@llu.edu.
authors.forename: Hansel M
authors.initials: HM
authors.lastname: Fletcher
mesh_terms: D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000633:toxicity*; D018384:Oxidative Stress; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D004269:DNA, Bacterial; D014157:Transcription Factors; D006861:Hydrogen Peroxide