Evolution of Sequence Type 4821 Clonal Complex Hyperinvasive and Quinolone-Resistant Meningococci.

Area of Science:

• Microbiology
• Genomics
• Epidemiology

Background:

• Neisseria meningitidis clone China^{CC4821-R1-C/B}, belonging to sequence type (ST) 4821 clonal complex (CC4821), caused a serogroup shift in invasive meningococcal disease (IMD) in China.
• This clone is characterized by quinolone resistance and a shift from serogroup A to C.

Purpose of the Study:

• To investigate the global distribution and genetic relationships of CC4821 meningococci.
• To understand the evolutionary dynamics and potential pandemic threat of this specific clone.

Main Methods:

• Whole-genome sequencing of 173 CC4821 Neisseria meningitidis isolates.
• Phylogenetic analysis to cluster isolates into sublineages.
• Analysis of antimicrobial resistance markers and serogroup-associated genes.

Main Results:

• CC4821 meningococci clustered into four distinct sublineages.
• Sublineage 1 predominantly consisted of IMD isolates (82%).
• A distinct Europe-USA cluster (sublineage 2) comprised 81.6% of non-China isolates, featuring the B:P1.17-6,23:F3-36:ST-3200 strain with penicillin-binding protein 2 mutations.

Conclusions:

• The quinolone-resistant Neisseria meningitidis clone China^{CC4821-R1-C/B} has expanded internationally.
• The global spread of serogroup B CC4821 raises concerns about its pandemic potential.
• While challenging to control, the Trumenba vaccine may offer some protection against this emerging threat.