Brucella hijacks host-cell-mediated palmitoylation to stabilize and localize PrpA to the plasma membrane

SPERA, J.M.; UGALDE, J.E.; CORVI, MM; GUAIMAS, F.

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2018 vol. 86

0019-9567

Brucellaceaeare a group of pathogenic intracellular bacteria with the ability to modulatethe host response, both at the individual cell level and systemically. One ofthe hallmarks of the virulence process is the capacity of the bacteria todownregulate the adaptive and acquired host immune response through a plethoraof virulence factors that directly impact several key signaling cascades. PrpAis one of those virulence factors that alters, via its polyclonal B-cellactivity, the humoral and cellular immune responses of the host, ultimatelyfavoring the establishment of a chronic infection. Even though PrpA affectsB-cells, it directly targets macrophages, triggering a response that ultimatelyaffects B-lymphocytes. In the present manuscript we report that PrpA isS-palmitoylated in two N-terminal cysteine residues by the host cell and thatthis modification is necessary for its biological activity. Our results demonstratethat S-palmitoylation promotes the migration or PrpA to the host cell membraneand stabilizes the protein during infection. These findings add a new mechanismexploited by this highly evolved pathogen to modulate the host immune response.