Project description:In order to promote intracellular survival and infection, Legionella spp. translocate hundreds of effector proteins into eukaryotic host cells using a type IV b protein secretion system (T4bSS). T4bSS are well known to translocate soluble as well as transmembrane domain-containing effector proteins (TMD-effectors) but the mechanisms of secretion are still poorly understood. Herein we investigated the secretion of hydrophobic TMD-effectors, of which about 80 were previously reported to be encoded by L. pneumophila. A proteomic analysis of fractionated membranes revealed that TMD-effectors are targeted to and inserted into the bacterial inner membranes of L. pneumophila independent of the presence of a functional T4bSS. While the T4bSS chaperones IcmS and IcmW were critical for secretion of all tested TMD-effectors, they did not influence inner membrane targeting of these proteins. The translocation of TMD-effectors into host cells proved to be dependent on a C-terminal secretion signal as it is the case for soluble effector proteins and this signal required presentation towards the cytoplasmic side of the inner membrane. A differential secretion behavior of TMD- and soluble effectors and a need for small periplasmic loops within TMD-effectors provided strong evidence that TMD-effectors are secreted in a two-step secretion process with an inner membrane intermediate that is extracted towards the cytoplasm, possibly by aid of the type IV coupling protein complex, for subsequent secretion into eukaryotic host cells by the T4bSS core complex. Overall, our study highlights the amazing versatility of T4bSS to secrete soluble and TMD-effectors from different subcellular locations of the bacterial cell.

2024-10-15 | PXD050153 | Pride

A Legionella pneumophila-translocated substrate that is required for growth within macrophages and protection from host cell death.

Project description: Not available

| S-EPMC1656969 | biostudies-literature

Native structure of a type IV secretion system core complex essential for Legionella pathogenesis.

Project description: Not available

| S-EPMC4136560 | biostudies-literature