Journal Article

Legionella and Coxiella effectors: strength in diversity and activity

Luo, Zhao-Qing, Qiu, Jiazhang

2017

Overview

Key Points Legionella pneumophila and Coxiella burnetii are two evolutionarily related intracellular bacterial pathogens that reside in distinct compartments in host cells during infection. Successful infection by both pathogens requires a functionally exchangeable type IV secretion system called Dot/Icm, which translocates hundreds of virulence factors, termed effectors, into host cells. The majority of Legionella spp. and Coxiella spp. effectors are unique to these pathogens, and functional redundancy exists among many of them. Functional domains that are associated with most of these effectors are enigmatic and cannot be readily predicted by currently available bioinformatics tools. Legionella spp. and Coxiella spp. promote intracellular bacterial replication by interfering with host gene expression through effectors that impose epigenetic modifications on host chromatin by different mechanisms. L. pneumophila extensively manipulates the early phases of the secretory branch of the host vesicle trafficking pathway by hijacking the activity of key regulatory proteins such as RAB small GTPases via multiple effectors. L. pneumophila effectors function coordinately to alter the composition of lipids, such as phosphoinositides, on the vacuole that contains the bacterium and other organelles to facilitate its intracellular growth. L. pneumophila co-opts the ubiquitin network of host cells by effectors that function through diverse biochemical mechanisms, including the SidE family effectors, which catalyse ubiquitylation by an E1 enzyme and E2 enzyme-independent mechanism, which represents a paradigm shift in our understanding of this important post-translational modification. The intracellular pathogens Legionella pneumophila and Coxiella burnetii use the Dot/Icm type IV secretion system to translocate effectors into host cells. Qiu and Luo explore the biochemical and cell biological functions of these effectors and their roles in our understanding of bacterial virulence. Legionella pneumophila and Coxiella burnetii are two evolutionarily related intracellular pathogens that use the Dot/Icm type IV secretion system to translocate effectors into host cells. These effectors are essential for the establishment of membrane-bound compartments known as replication vacuoles, which enable the survival and replication of bacteria inside host cells. The effectors interfere with diverse signalling pathways to co-opt host processes, such as vesicle trafficking, ubiquitylation, gene expression and lipid metabolism, to promote pathogen survival. In this Review, we explore Dot/Icm effectors from L. pneumophila and C. burnetii as key virulence factors, and we examine the biochemical and cell biological functions of these effectors and their roles in our understanding of bacterial virulence.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/41/2180 / 631/326/41/2531 / 631/326/41/2534 / 631/326/41/88 / 631/326/421 / 631/45/607 / Bacteria / Bacterial proteins / Biological Transport - physiology / Coxiella burnetii - genetics / Coxiella burnetii - metabolism / Coxiella burnetii - pathogenicity / Effectors / Gene expression / Gene Expression - genetics / Genetic aspects / Health aspects / Infectious Diseases / Legionella / Legionella pneumophila / Legionella pneumophila - genetics / Legionella pneumophila - metabolism / Legionella pneumophila - pathogenicity / Legionnaires' disease bacterium / Life Sciences / Lipid metabolism / Lipid Metabolism - physiology / Lipids / Medical Microbiology / Microbiology / Parasitology / Pathogens / Protein binding / Replication / review-article / Rickettsiae / Secretion / Signal transduction / Survival / Type IV Secretion Systems - physiology / Ubiquitin / Ubiquitin-Protein Ligases - metabolism / Ubiquitination / Vacuoles / Vacuoles - microbiology / Virology / Virulence / Virulence (Microbiology) / Virulence factors