Deciphering the Role of Respiratory Mucus in Neisseria meningitidis - Host Interactions: Impact of Temperature-Regulated Virulence Factors and Mucins

• Applicant: Professorin Dr. Alexandra Schubert-Unkmeir
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 558830896

Neisseria meningitidis is a Gram-negative pathogen that typically resides as a harmless commensal in the upper respiratory tract. However, under specific conditions, it can overcome the mucosal barrier and entering the bloodstream, causing severe diseases such as septicemia and meningitis. While the interaction with epithelial cells has been studied in detail, much less is known about how this pathogen traverses the respiratory mucus to initiate this invasion. Microbial pathogens employ diverse strategies to overcome mucosal barriers, such as transmigration through mucus via flagella, secretion of mucin-degrading enzymes, and downregulation of mucin synthesis. Using an air-liquid interface (ALI) culture model of a polarized, mucus-secreting epithelium, we observed that N. meningitidis efficiently transmigrates through the mucus at 32°C, the physiological temperature of the nasopharynx. This temperature-dependent increase in transmigration was particularly evident in hypervirulent isolates (MenB and MenW), where a small fraction of bacteria successfully penetrated the mucus and reached the epithelial surface without compromising barrier integrity. These findings suggest that specific temperature-regulated mechanisms enable N. meningitidis to overcome the mucus barrier, a critical step in the development of invasive disease. We will (1) identify temperature-regulated virulence factors that facilitate mucus penetration, (2) characterize the interaction between N. meningitidis and key gel-forming and cell-associated mucins (MUC5AC, MUC5B, MUC1, MUC4, MUC16), (3) perform RNA-sequencing analysis to analyze the global transcriptional response of N. meningitidis in conditions mimicking the nasopharyngeal environment. By understanding how N. meningitidis adapts to the nasopharyngeal environment and crosses the mucus barrier, this research will contribute to the broader field of microbial pathogenesis and host-pathogen interactions.

• DFG Programme: Research Grants