Gonococcal pilin variants in experimental gonorrhea

Area of Science:

• Microbiology
• Genetics
• Immunology

Background:

• Neisseria gonorrhoeae (Gc) is a bacterium that causes gonorrhea.
• Gc uses pili, protein filaments on its surface, for attachment and immune evasion.
• Pilin, the main component of pili, is a target for antibodies but exhibits antigenic variation.

Purpose of the Study:

• To investigate the genetic mechanisms underlying pilin antigenic variation in Gc.
• To identify the genomic regions involved in generating pilin diversity.
• To characterize the antigenic changes in Gc pilins resulting from genetic alterations.

Main Methods:

• Introduction of pilus+ Gc into a male subject's urethra.
• Analysis of pilin mRNA sequences in Gc variants.
• Identification of gene conversion events involving complete and partial pilin genes.
• Immunoblotting with monoclonal antibodies (mAbs) to detect antigenic differences in pilins.

Main Results:

• Gc variants exhibited altered pilin mRNA sequences compared to the input strain.
• These alterations resulted from gene conversion events between the complete pilin gene and various partial pilin genes.
• Some variants showed evidence of multiple independent gene conversion events.
• The resulting pilins displayed antigenic differences, detectable by mAbs.
• Amino acid and antigenic changes were observed in a previously conserved pilin segment.

Conclusions:

• Gene conversion involving partial pilin gene sequences is a key mechanism for generating pilin diversity in Gc.
• This process leads to antigenic variation in Gc pilins, potentially affecting immune responses.
• The findings reveal that a previously conserved pilin region is subject to genetic modification and antigenic change.