MODULATION OF CELL-SURFACE SIALIC-ACID EXPRESSION IN NEISSERIA-MENINGITIDIS VIA A TRANSPOSABLE GENETIC ELEMENT

Cell surface-located sialic acids of the capsule and the lipooligosacc haride (LOS) are both pivotal virulence factors in Neisseria meningiti dis, promoting survival and dissemination of this pathogen which can c ause both sepsis and meningitis, With the aid of a unique set of isoge nic meningococcal mutants defective in the expression of cell surface- located sialic acids, we have demonstrated that encapsulation hinders the primary event in the development of the disease, but the spontaneo us switching of encapsulated wild-type bacteria to a capsule-negative phenotype promotes meningococcal adherence and invasion into mucosal e pithelial cells, Genetic analysis of the capsule-negative, invasive ba cteria revealed a unique mechanism for modulation of capsule expressio n based on the reversible inactivation of an essential sialic acid bio synthesis gene, siaA, by insertion/excision of a naturally occurring i nsertion sequence element, IS1301, Inactivation of siaA regulates both capsule expression and endogenous LOS sialylation, This is the first example of an insertion sequence element-based genetic switch mechanis m in the pathogenic bacterium and is an important step in the understa nding of bacterial virulence.