Research on the roles of genes coding ATP‐binding cassette transporters in Porphyromonas gingivalis pathogenicity

Abstract

Porphyromonas gingivalis, as a major pathogen of periodontitis, could rapidly adhere to and invade host gingival epithelial cells (GECs) for the induction of infection. One ATP‐binding cassette (ABC) transporter gene was found to be upregulated during this infection process, however, the molecular mechanisms remain unclear. In this study, we systemically investigated the messenger RNA level changes of all ABC transporter family genes in P. gingivalis while being internalized within GECs by real‐time polymerase chain reaction. We identified that two ABC transporter genes, PG_RS04465 (PG1010) and PG_RS07320 (PG1665), were significantly increased in P. gingivalis after coculturing with GECs. Mutant strains with knockout (KO) of these two genes were generated by homogenous recombination. PG_RS04465 and PG_RS07320 KO mutants showed no change in the growth of bacteria per se. Knockdown of PG_RS07320, but not PG_RS04465, caused decreased endotoxin level in the bacteria. In contrast, both mutant strains showed decreased Arg‐ and Lys‐gingipains activities, with significantly reduced adhesion and invasion capabilities. Secreted interleukin‐1β (IL‐1β) and IL‐6 levels in GECs cocultured with PG_RS04465 or PG_RS07320 KO mutants were also decreased, whereas, only the cells cocultured with PG_RS07320 KO mutants showed significant decrease. In addition, virulence study using mouse revealed that both KO mutant strains infection caused less mouse death than wild‐type strains, showing reduced virulence of two KO strains. These results indicated that ABC transporter genes PG_RS04465 and PG_RS07320 are positive regulators of the virulence of P. gingivalis.

A GntR family transcription factor in Porphyromonas gingivalis regulates bacterial growth, acylpeptidyl oligopeptidase, and gingipains activity

“…A relationship between the production of PG1010 and PG1665 and gingipain activity was observed by Gao et al. (2020). In this study, pg1010 and pg1665 were significantly upregulated in the Δpg1007 mutant (Figure 4a).…”

“…It is worth noting that the gingipains in the supernatant here could be vesicle-bound protease and protease that is free in solution as the 0.2 μm filtration will not remove vesicles from the supernatant (Oishi et al, 2010). A relationship between the production of PG1010 and PG1665 and gingipain activity was observed by Gao et al (2020). In this study, pg1010 and pg1665 were significantly upregulated in the Δpg1007 mutant (Figure 4a).…”

Dysbiosis of Oral Microbiota and Metabolite Profiles Associated with Type 2 Diabetes Mellitus

“…Gao et al have reported that the ABC transporter genes PG_RS04465 and PG_RS07320 played an important role in the infection of gingival epithelial cells by Porphyromonas gingivalis . These results indicated that bacterial ABC transporters were essential for pathogenicity of Porphyromonas gingivalis ( 33 ). Therefore, we speculate that ABC transporters may be a clue in the pathogenesis of periodontal disease in patients with type 2 diabetes mellitus.…”

Virtual Screening to Identify Protein Targets of Aggregatibacter Actinomycetemcomitans Interacting with Emodin

“…The present study has been designed to identify the potential interactions with the protein targets with emodin. A study [32] reported the process of inhibition by reserpine where the phytocompound interacts with the transporters of red complex pathogens [33]. The proteins were found in the cytoplasm membrane of the bacteria [34].…”