Restriction-modification systems are required for Neisseria gonorrhoeae pilin antigenic variation

Abstract

Neisseria gonorrhoeae (Gc) pilin antigenic variation is a diversity-generating system that uses gene conversion to produce a variety of PilE protein variants, the major subunit of the Type IV pilus (T4p). Pilin antigenic variation allows the bacteria to escape immune surveillance and can alter T4p expression. While pilin antigenic variation requires many conserved homologous recombination and DNA repair factors, the pattern of sequence changes leading to pilin antigenic variants resembles that of an annealing reaction, rather than the expected long recombination tracts usually found in homologous recombination. We demonstrate that two paralogous restriction modification modules cleave specific, unmodified sequences within the expressed and silent pilin loci and that cleavage is essential for pilin antigenic variation. Moreover, these restriction activities affect the bacteriums fitness. These findings partially explain the patchwork recombination patterns of pilin antigenic variants and suggest a unique mechanism for generating diversity.