Neisseria prophage repressor implicated in gonococcal pathogenesis.

Area of Science:

• Microbiology
• Molecular Biology
• Pathogenesis

Background:

• Neisseria gonorrhoeae causes gonorrhea, a sexually transmitted infection affecting mucosal sites.
• Efficient colonization requires precise regulation of gene expression in response to environmental changes.

Purpose of the Study:

• To identify and characterize a novel gonococcal transcriptional regulatory protein, Neisseria phage repressor (Npr).
• To investigate the role of Npr in Neisseria gonorrhoeae adherence, invasion, and colonization.

Main Methods:

• Identification and characterization of the Npr protein.
• Construction and analysis of a gonococcal npr mutant.
• In vitro assays for adherence and invasion of human epithelial cells.
• In vivo colonization studies in a mouse model.
• RNA sequencing (RNA-seq) to determine the Npr regulon.

Main Results:

• Npr represses transcription of the NGNG_00460-00463 operon within the NgoΦ4 phage locus.
• Npr binding sites overlap key promoter elements (-10 and -35 motifs).
• An npr mutant showed significantly increased adherence to and invasion of human endocervical cells.
• The npr mutant exhibited enhanced mucosal colonization in a mouse model.
• RNA-seq confirmed the Npr regulon is restricted to the phage locus operon.

Conclusions:

• Npr is a novel gonococcal phage repressor protein.
• Npr plays a critical role in regulating genes associated with Neisseria gonorrhoeae pathogenesis.
• Npr controls bacterial adherence, invasion, and colonization, representing a potential therapeutic target.