Neisseria meningitidis poses a significant global health challenge, causing 0.5–1.2 million cases and 50 000–135 000 deaths annually. Adaptation of N. meningitidis to various human host microenvironments (e.g., the nasopharynx, or blood) is influenced by phase variation of several proteins, including phase-variable Type III DNA methyltransferases (Mods). Phase-variation of the Type III DNA methyltransferase, ModA11, has previously been shown to cause global changes in the N. meningitidis MC58 methylome, which alters the expression of multiple genes within the bacterial population. Notably, this differential gene expression is associated with various phenotypes, including resistance to antibiotics.
This study aims to characterise the effect of phase-variation of N. meningitidis MC58 ModA11 on recN expression, which has a ModA11 methylation site in its promoter region. RecN is involved in DNA repair and in protection against oxidative damage. To confirm ModA11 mediated regulation of recN, we developed a recN promoter-lacZ fusion construct, and transformed this reporter into N. meningitidis MC58 ModA11 ON and OFF strains at a complementation site between NMB1428 and NMB1429 genes. LacZ expression from the recN promoter in the presence or absence of ModA11 was then evaluated using a β-galactosidase activity assay. Site-directed mutagenesis of the ModA11 recognition site in the recN promoter is also underway to confirm the molecular mechanism of ModA11 epigenetic regulation of recN.
By investigating the impact of ModA11 methylation on recN expression in N. meningitidis, this study will further unravel the molecular mechanisms driving bacterial gene regulation while shedding light on bacterial adaptation mechanisms and fundamental aspects of bacterial epigenetics. Furthermore, this information will provide a foundation for developing targeted interventions to mitigate the impact of infectious diseases.