THE NEISSERIA TYPE-2 IGA1 PROTEASE CLEAVES LAMP1 AND PROMOTES SURVIVAL OF BACTERIA WITHIN EPITHELIAL-CELLS

Infection of human epithelial cells by Neisseria meningitidis (MC) and Neisseria gonorrhoeae (GC) increases the rate of degradation of LAMP1 , a major integral membrane glycoprotein of late endosomes and lysosom es. Several lines of evidence indicate that the neisserial IgA1 protea se is directly responsible for this LAMP1 degradation. LAMP1 contains an IgA1-like hinge region with potential cleavage sites for the neisse rial type 1 and type 2 IgA1 proteases. Neisserial type 2 IgA1 protease cleaves purified LAMP1 in vitro. unlike its wild-type isogenic parent , an iga(-) mutant of N. gonorrhoeae cannot affect LAMP1 turnover and its growth in epithelial cells is dramatically reduced. Thus, IgA1 pro tease cleavage of LAMP1 promotes intracellular survival of pathogenic Neisseria spp.