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

Abstract

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.