Neisseria meningitidis serogroup W ST-4821 clonal complex shares a highly conserved capsular switching pattern with ST-11 clonal complex strains

OBJECTIVES: Neisseria meningitidis ST-4821 clonal complex (cc4821) has become the most prevalent in China, which can be divided into four sublineages globally, with the L44.4 sublineage incorporating all serogroup W (MenW) cc4821 isolates. We aimed to illustrate the capsular switching that generated MenW cc4821 isolates, focused on the origin and the universal capsular switching pattern. METHODS: The nucleotide sequences of capsular polysaccharide synthesis (cps) gene cluster were extracted from the genomes of cc4821 L44.4 sublineage in the Neisseria PubMLST Database and analyzed using MEGA software. The capsular switching of MenC to MenW was conducted via natural transformation, and the infectivity was evaluated through in vitro experiments. RESULTS: Phylogenetic analysis on cps of cc4821 L44.4 indicated that MenW, MenC, and MenB isolates could be clearly distinguished only in region A. Nm464 performed PacBio sequencing for origin analysis, which identified a potential donor strain (W: P1.18-1,3: F4-1: ST-22 [cc22]). C→W capsular switching was performed ex vivo, with recombinant sequences being highly conserved between cc4821 and cc11 MenW isolates. The transformant expressed a similar level of capsular polysaccharides to the donor strain but grew more slowly than the recipient strain. CONCLUSIONS: C→W capsular switching with a cc22 strain as the potential donor was identified in cc4821 isolates, which is a highly conserved pattern among MenW strains. A fitness cost was found in the capsular switching.