Hemin availability induces coordinated DNA methylation and gene expression changes in Porphyromonas gingivalis

Area of Science:

• Microbiology
• Epigenetics
• Oral Health

Background:

• Periodontal disease is a chronic inflammatory condition linked to the oral pathogen Porphyromonas gingivalis.
• P. gingivalis virulence is known to be influenced by hemin availability, but regulatory mechanisms are unclear.
• Bacterial DNA methylation is a potential regulator of gene expression.

Purpose of the Study:

• To characterize the methylome of P. gingivalis.
• To investigate the relationship between DNA methylation and gene expression in response to varying hemin concentrations.
• To identify epigenetic mechanisms regulating P. gingivalis virulence in periodontal disease.

Main Methods:

• P. gingivalis W50 was cultured under conditions of excess and limited hemin.
• Whole-methylome profiling was performed using Nanopore technology.
• Transcriptome profiling was conducted using Illumina RNA-Seq.
• DNA methylation was quantified for specific motifs (Dam/Dcm) and general modifications (6mA, 5mC).

Main Results:

• Significant changes in gene expression were observed with excess hemin (161 over-expressed, 268 under-expressed genes).
• Differential DNA methylation signatures were detected for the Dam "GATC" motif, N6-methyladenine (6mA), and 5-methylcytosine (5mC) in response to hemin.
• Joint analysis revealed coordinated changes in gene expression and DNA methylation (6mA, 5mC) affecting genes involved in lactate utilization and ABC transporters.

Conclusions:

• Hemin availability significantly impacts both DNA methylation and gene expression in P. gingivalis.
• Altered DNA methylation patterns are linked to hemin-regulated virulence factor expression.
• These findings elucidate novel epigenetic regulatory mechanisms in P. gingivalis, contributing to understanding its role in periodontal disease.