Legionella pneumophilaexploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7

Abstract

SummaryL. pneumophilastrains harboring wild-typerpsLsuch as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The mechanism of this unique infection-induced cell death remains unknown. Using a genome-wide CRISPR/Cas9 screening, we identifiedHmg20aandNol9as host factors important for restricting strain Lp02rpsLWT in BMDMs. Depletion ofHmg20aprotects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed byHmg20awas mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02rpsLWT in BMDMs. Our results establish thatL. pneumophilaexploits the lysosomal network for the biogenesis of its phagosome in BMDMs.