Journal Article

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

Li, Chuang, Luo, Zhao-Qing, Shao, Shuai, Fu, Jiaqi

2024

Overview

Legionella pneumophila strains harboring wild-type rpsL such as Lp02 rpsL WT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The bacterial factor directly responsible for inducing such cell death and the host factor involved in initiating the signaling cascade that leads to lysosome damage remain unknown. Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a and Nol9 as host factors important for restricting strain Lp02 rpsL WT in BMDMs. Depletion of Hmg20a protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by Hmg20a was 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 Lp02 rpsL WT in BMDMs. Our results establish that L . pneumophila exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animals / Apoptosis / Autophagy / Bacteria / Bacterial infections / Biology and Life Sciences / Biosynthesis / Bone marrow / Care and treatment / Cell death / Chromosomal proteins / CRISPR / Damage / Diagnosis / Endosomes - metabolism / Endosomes - microbiology / Flow cytometry / Genes / Genetic aspects / Genomes / Genomics / Health aspects / Infection / Infections / Legionella pneumophila / Legionella pneumophila - genetics / Legionella pneumophila - metabolism / Legionnaires' Disease - metabolism / Legionnaires' Disease - microbiology / Legionnaires' disease bacterium / Lysosomes - metabolism / Lysosomes - microbiology / Macrophages / Macrophages - metabolism / Macrophages - microbiology / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Mutation / Pathogenesis / Pathogens / Phagosomes - metabolism / Phagosomes - microbiology / Protein synthesis / Proteins / rab GTP-Binding Proteins - metabolism / rab7 GTP-Binding Proteins / Research and Analysis Methods / Strains (organisms) / Sumoylation