[Molecular bases of virulence in Neisseria gonorrhoeae]

Gonorrhea remains of clinical concern, due to its frequency, complications, sequelae, increasing prevalence of antibiotic-resistant strains and absence of vaccine. A better understanding of the first stages of infection as well as of mechanisms of escape to immune response appears important. Many pathogenic bacteria express pili on their all surfaces. These structures mediate binding of bacteria to host tissues. Furthermore, gonococcal pili are submitted to a high rate antigenic variation, allowing the escape to host immune response. Pilin antigenic variation occurs by DNA recombination between one of the silent partial variant gene segments and an expressed pilin genes. We have shown that transformation of living bacteria by DNA liberated from lysed cells is a critical strep for antigenic variation. This constitutes the first specific function for a DNA transformation system. Piliation and virulence can change with culture conditions. This observation suggests that pilin expression would be subjected to an adaptative response. We have identified and characterized two genes which act in trans to regulate pilus expression. They determine synthesis of a response regulator and a membrane located sensor. They appear to regulate expression of other genes, possibly also involved in virulence. We present evidence for several environmental factors which may control the degree of piliation.