Multiple protein differences exist between Neisseria gonorrhoeae type 1 and type 4.

Neisseria gonorrhoeae undergoes a spontaneous conversion from a form which is virulent, competent for DNA-mediated transformation, and piliated (type 1) to a form which is avirulent and neither piliated nor competent (type 4). This phase variation has become thought of as simply a conversion from piliated to nonpiliated. Using the techniques of cell fractionation, two-dimensional electrophoresis, and nonequilibrium pH gradient gel electrophoresis, we identified differences in the expression levels of multiple proteins between type 1 and type 4 cells. A total of 26 type 1-specific (T1S) and 23 type 4-specific (T4S) cytoplasmic or cytoplasmic membrane proteins were identified in O'Farrell two-dimensional gels. Using nonequilibrium pH gradient gel electrophoresis, we detected a minimum of eight T1S outer membrane proteins and four T4S outer membrane proteins which were not detected in the O'Farrell gels. Thus, the conversion from type 1 to type 4 is a complex event involving many different proteins of all cellular locations.