Journal Article

Molecular pathogenesis of the obligate intracellular bacterium Coxiella burnetii

Mertens, Katja, van Schaik, Erin J., Chen, Chen, Samuel, James E., Weber, Mary M.

2013

Overview

Key Points Coxiella burnetii is a Gram-negative obligate intracellular bacterial pathogen that is the aetiological agent of Q fever, which manifests as both acute and chronic infections. The infection is a zoonosis that is most often transmitted by aerosolized dry, contaminated soil or animal products. Genetic differences between C. burnetii isolates from acute and chronic infections have led to the hypothesis that pathotype-specific virulence exists. After inhalation by a host, C. burnetii invades and replicates within alveolar macrophages without alerting the innate immune system and has therefore been described as a stealth pathogen. Inside macrophages, the bacterium replicates within a compartment that is very similar to a phagolysosome, termed the Coxiella -containing vacuole (CCV). C. burnetii has a type IV secretion system that resembles the Dot/Icm (defect in organelle trafficking/intracellular multiplication) system of Legionella pneumophila and is necessary for pathogenesis. C. burnetii encodes homologues for 24 of the 27 L. pneumophila Dot/Icm proteins, and four C. burnetii Dot/Icm genes can actually complement homologous mutations in the L. pneumophila system, lending strength to the conjecture that these systems are structurally and functionally similar. Establishment and maintenance of the CCV is dependent on protein production by C. burnetii . Although the identity of the virulence factors involved are unknown, new evidence suggests that most are effectors secreted by the type IV secretion system. The recent development of axenic media to grow C. burnetii has enabled the development of genetic tools to identify virulence factors. These developments have started a new era of research for C. burnetii , and Koch's postulates can now be tested for the first time. The obligate intracellular bacterium Coxiella burnetii causes both acute and chronic zoonotic infections. Here, Samuel and colleagues discuss the recent technological advances that have facilitated a deeper understanding of the molecular mechanisms of C. burnetii pathogenesis, including host cell invasion and modulation by virulence factors exported through the type IV Dot/Icm secretion system. The agent of Q fever, Coxiella burnetii , is an obligate intracellular bacterium that causes acute and chronic infections. The study of C. burnetii pathogenesis has benefited from two recent fundamental advances: improved genetic tools and the ability to grow the bacterium in extracellular media. In this Review, we describe how these recent advances have improved our understanding of C. burnetii invasion and host cell modulation, including the formation of replication-permissive Coxiella -containing vacuoles. Furthermore, we describe the Dot/Icm (defect in organelle trafficking/intracellular multiplication) system, which is used by C. burnetii to secrete a range of effector proteins into the host cell, and we discuss the role of these effectors in remodelling the host cell.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 41 / Animals / Apoptosis / Bacteria / Bacterial Adhesion / Bacterial infections / Chronic illnesses / Coxiella burnetii / Coxiella burnetii - genetics / Coxiella burnetii - pathogenicity / Effectiveness / Epidemics / Epidemiology / Fever / Genetic engineering / Hepatitis / Host-Pathogen Interactions / Humans / Infections / Infectious Diseases / Integrin alphaVbeta3 - genetics / Integrin alphaVbeta3 - metabolism / Intracellular Membranes - metabolism / Intracellular Membranes - microbiology / Life Sciences / Medical Microbiology / Microbiology / Parasitology / Pathogenesis / Pathogens / Phagocytosis / Phagosomes - metabolism / Phagosomes - microbiology / Public health / Q Fever - microbiology / review-article / Time Factors / Vacuoles - microbiology / Virology / Virulence / Zoonoses