A Screen of Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole Biogenesis

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Coxiella burnetii is the causative agent of the human disease Q fever. This bacterium uses the Dot/Icm type IV secretion system to deliver effectors into the cytosol of host cells. The Dot/Icm system is required for intracellular replication of C. burnetii. To determine the contribution of individual proteins to the establishment of a vacuole that supports C. burnetii replication, we conducted a visual screen on a library of C. burnetii transposon insertion mutants and identified genes required for distinct stages of intracellular replication. This approach was validated through the identification of intracellular replication mutants that included insertions in most of the dot and icm genes, and through the identification of individual effector proteins delivered into host cell by the Dot/Icm system that participate in creating a vacuole that supports intracellular replication of C. burnetii. Complementation studies showed convincingly that the effector Cig57 was critical for intracellular replication. The effector protein Cig2 was found to play a unique role in promoting homotypic fusion of C. burnetii vacuoles. Disrupting host autophagy phenocopied the defect displayed by the cig2 mutant. Thus, our visual screen has successfully identified effectors required for intracellular replication of C. burnetii and indicates that Dot/Icm-dependent subversion of host autophagy promotes homotypic fusion of CCVs.

Vyšlo v časopise: A Screen of Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole Biogenesis. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004286
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004286

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