Modulation of Virulence by a Novel SPI-2 Injectisome Effector That Interacts with the Dystrophin-associated Protein Complex

Importance: In , the injectisome machinery encoded by pathogenicity island 2 (SPI-2) is conserved among the five subspecies and delivers proteins (effectors) into host cells, which are required for virulence. The identification and functional characterization of SPI-2 injectisome effectors advance our understanding of the interplay between and its host(s). Using an optimized method for preparing secreted proteins and a clinical isolate of the invasive non-typhoidal serovar Enteritidis strain D24359, we identified 22 known SPI-2 injectisome effectors and one new effector-SseM. SseM modulates bacterial growth during murine infection and has a sequence corresponding to a postsynaptic density-95/discs large/zonula occludens-1 (PDZ)-binding motif that is essential for interaction with the PDZ-containing host protein β-2-syntrophin and other components of the dystrophin-associated protein complex (DAPC). To our knowledge, SseM is unique among effectors in containing a functional PDZ-binding motif and is the first bacterial protein to target the DAPC.