Role of the Porphyromonas gingivalis iron-binding protein PG1777 in oxidative stress resistance.

Whole genome sequencing of the response of Porphyromonas gingivalis W83 to hydrogen peroxide revealed an upregulation of several uncharacterized, novel genes. Under conditions of prolonged oxidative stress in P. gingivalis, increased expression of a unique transcriptional unit carrying the grpE, dnaJ and three other hypothetical genes (PG1777, PG1778 and PG1779) was observed. The transcriptional start site of this operon appears to be located 91 bp upstream of the translational start, with a potential -10 region at -3 nt and a -35 region at -39 nt. Isogenic P. gingivalis mutants FLL273 (PG1777 : : ermF-ermAM) and FLL293 (PG1779 : : ermF-ermAM) showed increased sensitivity to and decreased survival after treatment with hydrogen peroxide. P. gingivalis FLL273 showed a fivefold increase in the formation of spontaneous mutants when compared with the parent strain after exposure to hydrogen peroxide. The recombinant PG1777 protein displayed iron-binding properties when incubated with FeSO4 and Fe(NH4)2(SO4).6H2O. The rPG1777 protein protected DNA from degradation when exposed to hydrogen peroxide in the presence of iron. Taken together, the data suggest that the grpE-dnaJ-PG1777-PG1778-PG1779 transcriptional unit may play an important role in oxidative stress resistance in P. gingivalis via its ability to protect against DNA damage.

Differential response of Porphyromonas gingivalis to varying levels and duration of hydrogen peroxide-induced oxidative stress.

Porphyromonas gingivalis, an anaerobic oral pathogen implicated in adult periodontitis, can exist in an environment of oxidative stress. To evaluate its adaptation to this environment, we have assessed the response of P. gingivalis W83 to varying levels and durations of hydrogen peroxide (H(2)O(2))-induced stress. When P. gingivalis was initially exposed to a subinhibitory concentration of H(2)O(2) (0.1 mM), an adaptive response to higher concentrations could be induced. Transcriptome analysis demonstrated that oxidative stress can modulate several functional classes of genes depending on the severity and duration of the exposure. A 10 min exposure to H(2)O(2) revealed increased expression of genes involved in DNA damage and repair, while after 15 min, genes involved in protein fate, protein folding and stabilization were upregulated. Approximately 9 and 2.8% of the P. gingivalis genome displayed altered expression in response to H(2)O(2) exposure at 10 and 15 min, respectively. Substantially more genes were upregulated (109 at 10 min; 47 at 15 min) than downregulated (76 at 10 min; 11 at 15 min) by twofold or higher in response to H(2)O(2) exposure. The majority of these modulated genes were hypothetical or of unknown function. One of those genes (pg1372) with DNA-binding properties that was upregulated during prolonged oxidative stress was inactivated by allelic exchange mutagenesis. The isogenic mutant P. gingivalis FLL363 (pg1372 : : ermF) showed increased sensitivity to H(2)O(2) compared with the parent strain. Collectively, our data indicate the adaptive ability of P. gingivalis to oxidative stress and further underscore the complex nature of its resistance strategy under those conditions.

Oxidative stress resistance in Porphyromonas gingivalis.

Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the periodontal pocket implies that this organism has properties that will facilitate its ability to respond and adapt to oxidative stress. Because the stress response in the pathogen is a major determinant of its virulence, a comprehensive understanding of its oxidative stress resistance strategy is vital. We discuss multiple mechanisms and systems that clearly work in synergy to defend and protect P. gingivalis against oxidative damage caused by reactive oxygen species. The involvement of multiple hypothetical proteins and/or proteins of unknown function in this process may imply other unique mechanisms and potential therapeutic targets.

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis.

Porphyromonas gingivalis, a major periodontal pathogen, must acquire nutrients from host derived substrates, overcome oxidative stress and subvert the immune system. These activities can be coordinated via the gingipains which represent the most significant virulence factor produced by this organism. In the context of our contribution to this field, we will review the current understanding of gingipain biogenesis, glycosylation, and regulation, as well as discuss their role in oxidative stress resistance and apoptosis. We can postulate a model, in which gingipains may be part of the mechanism for P. gingivalis virulence.