| Summary: | Studies are showing that the stress hormone cortisol can reach high levels in the gingival sulcus and induce shifts in the metatranscriptome of the oral microbiome. Interestingly, it has also been shown that cortisol can influence expression levels of Type IX Secretion System (T9SS) genes involved in gliding motility in bacteria belonging to the phylum Bacteroidota. The objective of this study was to determine if cortisol impacts gene expression and surface translocation of <i>Porphyromonas gingivalis</i> strain W50. To conduct these experiments, <i>P. gingivalis</i> was stabbed to the bottom of soft agar plates containing varying cortisol concentrations (0 μM, 0.13 μM, 1.3 μM, and 13 μM), and surface translocation on the subsurface was observed after 48 h of incubation. The results show that when grown with certain nutrients, i.e., in rich medium with the addition of sheep blood, lactate, or pyruvate, cortisol promotes migration of <i>P. gingivalis</i> in a concentration-dependent manner. To begin to examine the underlying mechanisms, quantitative PCR was used to evaluate differential expression of genes when <i>P. gingivalis</i> was exposed to cortisol. In particular, we focused on differential expression of T9SS-associated genes, including <i>mfa5,</i> since it was previously shown that Mfa5 is required for cell movement and cell-to-cell interactions. The data show that <i>mfa5</i> is significantly up-regulated in the presence of cortisol. Moreover, an <i>mfa5</i> deletion mutant showed less surface translocation compared to the wild-type <i>P. gingivalis</i> in the presence of cortisol, and the defects of the <i>mfa5</i> deletion mutant were restored by complementation. Overall, cortisol can stimulate <i>P. gingivalis</i> surface translocation and this coincides with higher expression levels of T9SS-associated genes, which are known to be essential to gliding motility. Our findings support a high possibility that the stress hormone cortisol from the host can promote surface translocation and potentially virulence of <i>P. gingivalis</i>.
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