Porphyromonas gingivalis is a Gram-negative, anaerobic bacterium considered to be an important pathogen of periodontal disease that is also implicated in adverse pregnancy outcome (APO). Until recently, our understanding of the role of P. gingivalis in APO has been limited and sometimes contradictory. The purpose of this review is to provide an overview of past and current research on P. gingivalis that addresses some of the controversies concerning the role of this organism in the pathogenesis of APO.

Porphyromonas gingivalis is an anaerobic bacterium commonly found in the oral cavity and associated with the development of periodontal disease. P. gingivalis has also been linked to several systemic vascular and inflammatory diseases including poor pregnancy outcomes. Little is known about the changes in the oral flora during pregnancy in connection to P. gingivalis infection. This pilot study aims to explore changes in the oral microbiome due to P. gingivalis inoculation and pregnancy in an in vivo rat model of periodontal disease. A metagenomic sequencing analysis targeting seven of the 16S rRNA gene variable regions was performed for oral samples collected at the following time points: baseline control (week 0), P. gingivalis inoculated (week 11), P. gingivalis inoculated and pregnant rat at necropsy (week 16). A second set of animals were also sampled to generate a sham-inoculated (week 11) control group. We found that the rat oral microbiome profiles were more similar to that of the human oral cavity compared to previous reports targeting one or two 16S variable regions. Overall, there appears to be a relatively stable core microbiome in the oral cavity. As expected, P. gingivalis induced periodontal disease resulted in oral microbiome dysbiosis. During pregnancy, some aspects of the oral microbiome shifted toward a more baseline-like profile. However, population analyses in terms of dissimilarity measures and especially metagenomic based predictions of select characteristics such as cell morphology, oxygen requirement, and major metabolite synthesis showed that pregnancy did not restore the composition of the oral microbiome. Rather, a uniquely altered oral microbiome composition was observed in pregnant rats with pre-established periodontal disease.

The oral obligate anaerobe Porphyromonas gingivalis possesses a small conserved transcript PG_RS02100 of unknown function we previously identified using small RNA-seq analysis as expressed during logarithmic growth. In this study, we sought to determine if PG_RS02100 plays a role in P. gingivalis growth or stress response. We show that a PG_RS02100 deletion mutant’s (W83Δ514) ability to grow under anaerobic conditions was no different than wildtype (W83), but it was better able to survive hydrogen peroxide exposure when cultured under heme limiting growth conditions, and was more aerotolerant when plated on enriched whole blood agar and exposed to atmospheric oxygen. Together, these results indicate that PG_RS02100 plays a role in surviving oxidative stress in actively growing P. gingivalis and that P. gingivalis’ response to exogenous hydrogen peroxide stress is linked to heme availability. Relative qRT-PCR expression analysis of oxyR, trx-1, tpx, sodB, ahpC, dinF, cydB, and frd, in W83Δ514 and W83 in response to 1 h exogenous dioxygen or hydrogen peroxide exposure, when cultured with varying heme availability, support our phenotypic evidence that W83Δ514 has a more highly primed defense system against exogenous peroxide, dioxygen, and heme generated ROS. Interestingly, W83Δ514 turned black faster than W83 when cultured on whole blood agar, suggesting it was able to accumulate heme more rapidly. The mechanism of increased heme acquisition observed in W83Δ514 is not yet known. However, it is clear that PG_RS02100 is involved in modulating the P. gingivalis cell surface in a manner related to survival, particularly against oxidative stress.

The Porphyromonas gingivalis type 9 secretion system (T9SS) is known for secreting and anchoring protein cargos to the outer surface of the bacterium, which are then selectively packaged into outer membrane vesicles. We previously identified a link between P. gingivalis ‐mediated dysregulated aortic smooth muscle cell (AoSMC) plasticity with binding of T9SS outer protein, PorU and select T9SS cargos to AoSMC proteins. To assess the role of T9SS in dysregulated AoSMC plasticity, a PorU ‐deficient mutant was constructed in P. gingivalis strain A7UF. AoSMC was inoculated with sterile vehicle, wild‐type A7UF, or A7UFΔPorU and evaluated for proliferation, migration, and changes in the TGF‐β/Smad2/3 signaling axis. Deletion of PorU disrupted T9SS function in P. gingivalis A7UF. Loss of T9SS function impaired P. gingivalis invasion and persistence in AoSMC as well as attenuated microbial‐induced effects on AoSMC plasticity. Specifically, direct T9SS/AoSMC interactions were necessary for P. gingivalis ‐induced AoSMC proliferation. Clarified supernatant from A7UF impaired the migration of infected AoSMC. P. gingivalis T9SS function was perturbed AoSMC TGF‐β/Smad3 signaling. Specifically, A7UF‐inoculated cells had increased linker and carboxy‐terminal phosphorylation of Smad3 that was attenuated in AoSMC inoculated with A7UFΔPorU. In summary, PorU and/or T9SS cargo play a role in P. gingivalis ‐induced dysregulation of AoSMC plasticity as well as TGF‐β/Smad signaling. Microbial manipulation of host cell signaling events is important for cell differentiation and tissue remodeling and would constitute a new virulence function for T9SS.