Pathogenicity variation of CC4821 Neisseria meningitidis in China from 2005 to 2024

Neisseria meningitidis (N. meningitidis) is the causative agent of invasive meningococcal disease (IMD). In China, clonal complex 4821 (CC4821) has become the predominant lineage of N. meningitidis over the past two decades. However, the differences in pathogenicity between CC4821 serogroups B and C strains remain unexplored. This study evaluated the distribution and pathogenicity of CC4821 isolates collected between 2005 and 2024 based on sources, serogroups, and time of isolation, including adhesion and invasion, and the ability to induce inflammatory responses and apoptosis. Results showed a significant increase in the recent prevalence of serogroup B isolates and enhanced adhesion and invasion abilities, whereas serogroup C isolates decreased significantly in number and decreased adhesion and invasion abilities. Inflammatory cytokine assays showed that all CC4821 isolates could induce the release of IL-6, IL-8, and TNF-α, with no notable differences between serogroups. Apoptosis assays indicated that recent invasive isolates of serogroups B and C had a significantly increased ability to induce apoptosis compared to earlier isolates, whereas carriage isolates consistently induced high levels of apoptosis in A549 cells. In conclusion, serogroup B strains have enhanced their respiratory tract colonization and transmission capabilities, while serogroup C strains, although their adhesion and colonization abilities have weakened, still pose potential risks. This underscores the necessity of continuous surveillance of both serogroup B and C strains, particularly focusing on asymptomatic carriers who may harbor high-risk variants.