Neisseria gonorrhoeae PilC expression provides a selective mechanism for structural diversity of pili

Pili of Neisseria gonorrhoeae undergo both phase and structural variation. Phase variation of gonococcal pili can be caused by a RecA-independent on/off switch in PilC, a protein involved in pilus biogenesis. We show here that spontaneous nonpiliated PilC^- derivatives as well as PilC^- insertional mutants have also acquired sequence alterations in pilE relative to the pilE gene of the piliated MS11(mk)(P⁺)-u parent, so that the pilin produced is processed to soluble S-pilin and can be released into the medium. It is proposed that pilin alterations are selected for in PilC^- bacteria if the parental nonassembled pilin is toxic to the cells-i.e., is not degradable to S-pilin at rates sufficient to allow viability of the cells. Toxicity is indicated by the extreme instability of certain unassembled pilin sequences and by the low frequency of nonpiliated, pilin⁺, PilC^- variants that emerge from piliated recA^- cells. The presence of a point mutation changing leucine-39 to phenylalanine at the cleavage site for S-pilin in one nonpiliated, PilC^-, recA^- variant relative to its piliated parent is a further argument for a selective mechanism of structural diversity of the gonococcal pilin.