Pilus-mediated co-aggregation with Lactobacillus crispatus increases meningococcal susceptibility to antimicrobial agents by interfering with microcolony formation

Abstract

Background: Neisseria meningitidis asymptomatically colonizes the nasopharyngeal mucosa, but occasionally, the bacteria disseminate to cause sepsis and meningitis. In the epithelial cell layer, the pathogen co-colonizes with other resident inhabitants, such as Lactobacillus species that are part of the nasopharyngeal-oral microbiota. In this study, we investigated the interaction between lactobacilli and meningococci. Results: We demonstrated that Lactobacillus crispatus strain MV24 can co-aggregate with meningococci, whereas all other Lactobacillus strains tested did not co-aggregate. The binding ability of L. crispatus was not strain- or serogroup-specific but was dependent on the ability of meningococci to form microcolonies. The finding that N. meningitidis lacking pili did not co-aggregate with L. crispatus, but that hyperpiliated N. meningitidis exhibited strong co-aggregation, led us to examine the interaction between purified meningococcal pili and lactobacilli. Our results showed that L. crispatus MV24 can bind to purified meningococcal Class I and II pili, explaining the aggregative clusters observed under the microscope. Co-aggregation with L. crispatus disrupted microcolony formation, and increased the killing of meningococci by LL-37, hBD2 and cephalexin. Further, co-aggregation had the added effect of impeding motility. Conclusion: N. meningitidis pili bind to L. crispatus, which interferes with the meningococcal microcolonies and increases sensitivity to antimicrobial agents. Taken together, our findings suggest that L. crispatus MV24 may have a beneficial effect on the host through co-aggregating with meningococci.