Creating a customized intracellular niche: subversion of host cell signaling byLegionellatype IV secretion system effectors

Abstract

Abstract:The Gram-negative facultative intracellular pathogen Legionella pneumophila infects a wide range of different protozoa in the environment and also human alveolar macrophages upon inhalation of contaminated aerosols. Inside its hosts, it creates a defined and unique compartment, termed the Legionella-containing vacuole (LCV), for survival and replication. To establish the LCV, L. pneumophila uses its Dot/Icm type IV secretion system (T4SS) to translocate more than 300 effector proteins into the host cell. Although it has become apparent in the past years that these effectors subvert a multitude of cellular processes and allow Legionella to take control of host cell vesicle trafficking, transcription, and translation, the exact function of the vast majority of effectors still remains unknown. This is partly due to high functional redundancy among the effectors, which renders conventional genetic approaches to elucidate their role ineffective. Here, we review the current knowledge about Legionella T4SS effectors, highlight open questions, and discuss new methods that promise to facilitate the characterization of T4SS effector functions in the future.Key words: Legionella, type IV secretion system, effectors, Legionella-containing vacuole.Résumé : Le pathogène intracellulaire facultatif à Gram négatif Legionella pneumophila infecte une large gamme de différents protozoaires environnementaux de même que les macrophages alvéolaires humains des suites de l'inhalation d'aérosols contaminés. À l'intérieur de ses hôtes, il crée un compartiment précis et unique nommé vacuole contenant Legionella (« Legionella-containing vacuole », LCV) pour sa survie et sa multiplication. Afin d'établir une LCV, L. pneumophila utilise sont système de sécrétion de type IV (SST4) Dot/Icm, rendant possible la translocation de plus de 300 protéines effectrices dans la cellule hôte. Au cours des dernières années, on a établi que ces effecteurs subvertissent une multitude de processus cellulaires et permettent à Legionella de prendre le contrôle du trafic cellulaire, de la transcription et de la traduction. Or, la fonction exacte de la grande majorité des effecteurs est toujours inconnue. L'importante redondance fonctionnelle au sein des effecteurs explique en partie cette incertitude et invalide les approches génétiques conventionnelles adoptées pour élucider leur rôle. Dans le présent ouvrage, nous passons en revue les connaissances actuelles entourant les effecteurs SST4 de Legionella, faisons ressortir certaines interrogations, et abordons de nouvelles méthodes qui promettent de faciliter la caractérisation de la fonction des effecteurs SST4. [Traduit par la Rédaction] Mots-clés : Legionella, système de sécrétion de type IV, effecteurs, vacuole contenant Legionella.

MTOR-Driven Metabolic Reprogramming Regulates Legionella pneumophila Intracellular Niche Homeostasis

“…Legionella species encode a type IVb secretion system (T4bSS), known as the Dot/Icm apparatus, which translocates over 300 bacterial effector proteins directly into the host cytosol [20–22]. The T4bSS is required for intracellular survival and deletion mutants lacking single structural components of the Dot/Icm apparatus are avirulent because they fail to block endocytic maturation [23–25].…”

“…The T4bSS is required for intracellular survival and deletion mutants lacking single structural components of the Dot/Icm apparatus are avirulent because they fail to block endocytic maturation [23–25]. Collectively, the Dot/Icm effector proteins facilitate niche biogenesis and homeostasis [20,22]. One example is the SdhA effector, which maintains LCV integrity by counteracting, through an unknown mechanism, the activity of the secreted Legionella phospholipase PlaA [18].…”

Space: A Final Frontier for Vacuolar Pathogens

“…rapidly depart the endocytic pathway by modifying their PV (called the inclusion) to resemble a Golgi-derived exocytic vacuole (23), further customizing it with a family of chlamydial proteins called Incs that mediate many crucial interactions with host signaling molecules and organelles (24). In contrast, the Legionella-containing vacuole (LCV) more closely resembles the ER, although its association with many different host Rab GTPases that are often not found on the same host membrane makes the LCV a distinctive subcellular compartment (25). Coxiella burnetii is a unique bacterial pathogen that replicates in what is essentially a mature phagolysosome (26).…”

Super-Resolution Imaging of Protein Secretion Systems and the Cell Surface of Gram-Negative Bacteria

“…The Dot/Icm machinery is the T4SS in Legionella spp. and is responsible for hundreds of effector proteins throughout the infection cycle (So et al, 2015). Epitope-tagging one of these effectors, LncP, enabled fluorescence imaging of infected macrophages and showed that the protein was secreted from the bacterial cytoplasm by the T4SS and ultimately translocated across a remarkable five membranes in order to be assembled into the mitochondrial inner membrane of the host cell (Dolezal et al, 2012).…”