Neisseria meningitidis biofilms: The role of capsule and two-partner secretion

Neisseria meningitidis is the etiologic agent of meningococcal meningitis. It is a common isolate of the human nasopharynx, present in approximately 10% of the population during endemic periods of infection. Carriers can be colonized for at least six months and can transmit the bacterium to close contacts during that time. Biofilm formation may serve as a mechanism by which the meningococcus could sustain the carrier state in the human nasopharynx and explain prolonged colonization. A biofilm is a community of bacteria on a surface, encased in an exopolymeric matrix. This community of bacteria is afforded better protection from immune defenses and environmental factors than an individual bacterium.;Our studies utilized a novel flow cell designed to accommodate a coverslip with a monolayer of transformed human airway epithial cells (HBE) on which biofilms could grow. Previous studies indicated that encapsulated meningococci could not form biofilms on plastic or glass surfaces. We determined that encapsulated meningococci can form mature biofilms on HBE cells and that these biofilms are significantly larger than biofilms grown on glass or collagen. We also confirmed that the organisms within the biofilm were encapsulated. A biofilm of encapsulated N. meningitidis could provide a population of bacteria more fit to traverse and survive within the intracellular environment and evade complement-mediated killing in the human host.;We extended our initial findings concerning N. meningitidis biofilms on HBE cells by investigating the role of the HrpA protein in biofilm formation. HrpA is the secreted component of a two-partner secretion system in N. meningitidis. Mutants of hrpA in N. meningitidis resulted in significantly reduced biofilm formation. Further analysis revealed up-regulation of the hrpA transcript in anaerobic conditions as well as with 5 hours of HBE cell association.;This study demonstrated the ability of N. meningitidis to form biofilms on HBE cells. Our findings help explain data from carriage studies and have implications in understanding meningococcal conjugate vaccine efficacy data in which nasopharyngeal carriage is reduced in vaccinated individuals. HrpA was revealed as a factor involved in biofilm formation and may be a target for future vaccine studies.