PILUS-MEDIATED ADHESION OF NEISSERIA-MENINGITIDIS - THE ESSENTIAL ROLE OF CELL CONTACT-DEPENDENT TRANSCRIPTIONAL UP-REGULATION OF THE PILC1PROTEIN

Pilus-mediated adherence makes an essential contribution to the pathog enesis of Neisseria meningitidis by allowing the initial localized adh erence, pill are assembled from a protein subunit called pilin, Two pr oteins, PilC1 and PilC2, are also key elements in the formation of pil i as the production of at least one PilC protein is required for pilus assembly. In addition, PilC1 but not PilC2 modulates adhesiveness, mo st probably by being the adhesin, Recently, both genes have been demon strated to be controlled by different promoters, pilC2 is expressed fr om a single transcription starting point (TSP), whereas pilC1 has thre e TSPs, One of these, PC1.1, corresponds to the unique TSP of pilC2, a nd two others, PC1.2 and PC1.3, are located in a region upstream of pi lC1 but not pilC2. This suggests that both genes may be under the cont rol of separate regulatory pathways. In this work, by engineering pilC 1-lacZ and pilC2-lacZ transcriptional fusions, we provide evidence tha t expression of pilC1, but not that of pilC2, is transiently induced b y bacterial cell contact, This induction required viable cells, did no t need the presence of pili and relied on the expression of pilC1 from PC1,3, Destruction of this TSP by site-directed mutagenesis did not s ignificantly diminish the piliation level or the basal expression of P ilC1, but led to the loss of cell contact-dependent upregulation of pi lC1 and to a dramatic decrease in bacterial adhesiveness. Taken togeth er, these data demonstrate that cell contact-dependent upregulation of the transcription of pilC1 at PC1.3 is essential for meningococcal pi lus-mediated adhesion.