CAPSULE SWITCHING OF NEISSERIA-MENINGITIDIS

The different sialic acid (serogroups B, C, Y, and W-135) and nonsiali c acid (serogroup A) capsular polysaccharides expressed by Neisseria m eningitidis are major virulence factors and are used as epidemiologic markers and vaccine targets. However, the identification of meningococ cal isolates with similar genetic markers but expressing different cap sular polysaccharides suggests that meningococcal clones can switch th e type of capsule they express. We identified, except for capsule, iso genic serogroups B [(alpha 2-->8)-linked polysialic acid] and C [(alph a 2-->9)-linked polysialic acid] meningococcal isolates from an outbre ak of meningococcal disease in the U. S. Pacific Northwest. We used th ese isolates and prototype serogroup A, B, C, Y, and W-135 strains to define the capsular biosynthetic and transport operons of the major me ningococcal serogroups and to show that switching from the B to C caps ule in the outbreak strain was the result of allelic exchange of the p olysialyltransferase. Capsule switching was probably the result of tra nsformation and horizontal DNA exchange in vivo of a serogroup C capsu le biosynthetic operon. These findings indicate that closely related v irulent meningococcal clones may not be recognized by traditional sero group-based surveillance and can escape vaccine-induced or natural pro tective immunity by capsule switching. Capsule switching may be an imp ortant virulence mechanism of meningococci and other encapsulated bact erial pathogens. As vaccine development progresses and broader immuniz ation with capsular polysaccharide conjugate vaccines becomes a realit y, the ability to switch capsular types may have important implication s for the impact of these vaccines.