The Quantity of G-Quadruplex in Bacterial Genome affects G-Quadruplex Ligand Sensitivity in Hypertension associated Tongue Coating Microbiota

Background Recently, more and more attention has been paid to the role of oral microbiota in hypertension. It was reported that the disorder of tongue coating microbiota would significantly increase systolic blood pressure, yet the characteristics of tongue coating microbiota of hypertensives remain unknown. Microbiota is regulated by genes, G-quadruplex (G4) is a secondary structure of nucleic acid, which plays an important role in the regulation of microbial biologic features. there are many G4 ligands in oral administration, but how G4 ligands affect the bacterial biological phenotype needs further exploration. Results We used metagenomics for analysis of 58 subjects including 23 healthy subjects and 35 hypertensives, and bioinformatics technology for detecting G4 characteristic sequences, finally verified by biological and chemical experiments. We found that Actinomyces decreased significantly in the hypertension group with the highest average maximum putative G-quadruplex forming sequences (PQS) and GC quantity. We also screened out two species with significantly different abundance between two groups, Actinomyces odontolyticus and Acinetobacter baumannii. A. odontolyticus had higher GC% and frequency of PQS per 1000bp in the genome, which led to differential inhibition of bacterial growth, metabolism, biofilm formation by G4 ligand, sanguinarine. Major Facilitator Superfamily (MFS) was found to be involved in these biological phenomena, we found that sanguinarine could bind and stabilize the G4 structure related to MFS and further inhibited the expression of MFS.ConclusionsDifferent quantities of G4 sequences in the bacterial genome affect G4 ligand sensitivity in hypertension-associated tongue coating species, A. odontolyticus and A. baumannii. G4 ligand (sanguinarine) can bind and stabilize the G4 characteristic sequence of the MFS gene to inhibit the expression, and then inhibit the growth, biofilm formation and metabolism. This study provides a theoretical basis for the selection of G4 based drugs in the oral cavity.