Effector Translocation by the Legionella Dot/Icm Type IV Secretion System

Abstract

Legionella pneumophila is an opportunistic pathogen responsible for Legionnaires' disease. This bacterium survives and replicates within phagocytes by bypassing their bactericidal activity. Intracellular replication of L. pneumophila requires the Dot/Icm type IV secretion system made of approximately 27 proteins that presumably traverses the bacterial and phagosomal membranes. The perturbation of the host killing ability largely is mediated by the collective functions of the protein substrates injected into host cells via the Dot/Icm transporter. Proper protein translocation by Dot/Icm is determined by a number of factors, including signals recognizable by the translocator, chaperones that may facilitate the proper folding of substrates and transcriptional regulation and protein stability that determine the abundance and temporal transfer of the substrates. Although a large number of Dot/Icm substrates have been identified, investigation to understand the translocation is ongoing. Here we summarized the recent advancements in our understanding of the factors that determine the protein translocation activity of the Dot/Icm transporter.

Regulation of Bacterial Virulence by Csr (Rsm) Systems

“…The T4SS structural genes are homologous to the T-DNA transfer system of Agrobacterium tumefaciens and the Tra transfer genes of the IncI ColIb-P9 plasmid of Shigella flexneri (205). The Dot/Icm complex includes approximately 27 protein components that are assembled into one of three subcomplexes: the inner membrane substrate receptor, the transmembrane bridge connecting the inner and outer core subcomplexes, and the outer membrane core containing the secretory components for host cell penetration (206). This T4SS secretes approximately 300 effectors (207)(208)(209)(210) and is important for intracellular replication, organelle trafficking, and effector-dependent egress from the host cell (204,(211)(212)(213).…”

Lysosomal degradation products induce Coxiella burnetii virulence

“…The C. burnetii Dot/Icm system is functionally analogous to the well-studied Dot/Icm system of Legionella species, which is essential for intracellular replication of Legionnaires' disease-causing pathogens (15). Despite depending on the same apparatus for virulence, the replicative niches of Legionella and C. burnetii are quite divergent.…”

Insights into the interactions of enterococcus faecalis with protozoan predators

“…pneumophilia utilises the Dot/Icm Type IV secretion system to modify the endosomal pathway and prevent bacterial cell digestion (Berk et al 2008, Hilbi, Segal, and Shuman 2001, Qiu and Luo 2014.…”

“…In general, extracellular pathogens seek to evade predation by altering their morphology, like forming filaments that are difficult to ingest (Hahn, Moore, and Höfle 1999), forming bacterial aggregates, microcolonies or biofilms to prevent phagocytosis (Hahn, Moore, and Hofle 2000), increasing motility to prevent capture (Matz and Jürgens 2005) or secretion of quorum sensing mediated toxic antipredator compounds (Matz, Bergfeld, et al 2004) Intracellular pathogens develop mechanisms to enhance their survival within protozoa. Some bacteria, such as Legionella pneumophilia, resist phagosomal digestion by using an elaborate Dot/Icm Type IV secretion system that secretes effectors that all the bacterium to persist within the host (Hilbi, Segal, andShuman 2001, Qiu andLuo 2014).…”

“…When ingested, bacteria are packaged into food vacuoles that become acidified and loaded with degradative enzymes. Undigested bacteria can stay within the protozoa without multiplication (Figure 1-1 A), or some bacteria such as Legionella pneumophila, which utilise the Dot/Icm Type IV secretion system to bypass the default phagosome maturation pathway and multiply within these specialised compartments (Hilbi, Segal, and Shuman 2001, Qiu and Luo 2014, Abu Kwaik et al 1998. Multiplication within protozoan hosts may eventually lead to cell lysis and dissemination of the bacteria.…”