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• W2971444372 abstract "Abstract Legionella pneumophila uses the Icm/Dot Type IV secretion system (T4SS) to translocate a record number (300) of bacterial effectors into the host cell. Despite recent breakthrough progress in determining the structure and the localization of the secretion machinery, it is still a challenge to understand how the delivery of so many effectors is organized to avoid bottleneck effect and to allow effective manipulation of the host cell by L. pneumophila. Here, we demonstrate that secretion of effectors is ordered and so precisely set up that it lines-up with the delivery timing required for the function of the effectors in the cell. We observe notably that the secretion order of 4 effectors targeting Rab1 is fully consistent with the sequence of their actions on Rab1. Importantly, we show that the timed delivery of an effector is not dependent on its concentration, nor on its picking-up by chaperone proteins. Conversely, this control involves c-di-GMP signaling, as a c-di-GMP synthesizing enzyme, namely the diguanylate cyclase Lpl0780/Lpp0809, significantly contributes to accurate triggering of effector secretion via a post-translational control of the T4SS machinery at the bacterial pole. Significance Type 3, 4 and 6 secretion systems are multiprotein complex known to be crucial for infectious cycle of many bacterial pathogens. Despite considerable progress on several fronts in structure-function analysis of these systems, one of the blackest boxes in our understanding is the signal that triggers the activation of effectors transfer. This is particularly true for the Icm/Dot T4SS in L. pneumophila that deals with the translocation of a record number of 300 effectors. We demonstrate that Icm/Dot secretion is timely fine-tuned and most importantly, that the complex orchestration of so many effector actions relies at least in part on the defined timing of their translocation into the host cell. Also, we highlight for the first time a post-translational control of a T4SS by c-diGMP signaling." @default.
• W2971444372 created "2019-09-12" @default.
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• W2971444372 date "2019-09-04" @default.
• W2971444372 modified "2023-09-26" @default.
• W2971444372 title "Orchestrated delivery of Legionella effectors by the Icm/Dot secretion system" @default.
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