Host Glycoprotein Gp96 and Scavenger Receptor SREC Interact with PorB of Disseminating Neisseria gonorrhoeae in an Epithelial Invasion Pathway

SummaryNeisseria gonorrhoeae expresses numerous surface proteins that mediate bacterial adherence and invasion during infection. Gonococci expressing serotype A of the major outer membrane porin PorB (PorBIA) are frequently isolated from patients with severe disseminating infections. PorBIA triggers efficient adherence and invasion under low phosphate conditions mimicking systemic bloodstream infections. Here, we identify the human heat shock glycoprotein Gp96 and the scavenger receptor SREC as PorBIA-specific receptors. Gonococci expressing PorBIA, but not those expressing PorB serotype B instead, bind to purified native or recombinant Gp96. Depletion of Gp96 from host cells prevented adherence but significantly triggered gonococcal invasion. Furthermore, such invasion was blocked by chemical inhibitors of scavenger receptors, and we identified SREC as the scavenger receptor involved in PorBIA-dependant invasion. Thus, we establish Gp96 as an anti-invasion factor and SRECs as receptors mediating host cell entry of highly invasive disseminating gonococci.