The Legionella longbeachae Icm/Dot Substrate SidC Selectively Binds Phosphatidylinositol 4-Phosphate with Nanomolar Affinity and Promotes Pathogen Vacuole-Endoplasmic Reticulum Interactions

Dolinsky, Stephanie; Haneburger, Ina; Cichy, Adam Leszek; Hannemann, Mandy; Itzen, Aymelt; Hilbi, Hubert

doi:10.1128/iai.01685-14

Cited by 54 publications

(48 citation statements)

References 63 publications

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“…Previous reports have suggested that the longbeachae-LCV is distinct from the pneumophila-LCV and that it associates with both early endosomal antigen 1 (EEA1) and lysosomal-associated membrane protein 2 (LAMP-2) (11). However, more recently it has been confirmed that the longbeachae-LCV formed in the amoebal host Dictyostelium discoideum is decorated with ER markers (16). We have clarified that the longbeachae-LCV is characteristically similar to the pneumophila-LCV by demonstrating that the longbeachae-LCV avoids endocytic maturation and acquisition of the late endosome and lysosome marker LAMP-1 in HEK 293T Fc␥R cells (Fig.…”

Section: Resultssupporting

confidence: 51%

“…SidC is a Dot/ Icm effector conserved in both L. pneumophila and L. longbeachae. As previously described in L. pneumophila, SidC localizes to the longbeachae-LCV in a Dot/Icm-dependent manner, and, in both organisms, SidC acts to promote ER recruitment to the LCV (16,37). Translocation of SidC was demonstrated using immunofluorescence microscopy and an antibody specific to SidC (16).…”

Section: Figmentioning

confidence: 60%

“…There is evidence to suggest that the longbeachae-LCV is distinct from the pneumophila-LCV (11). However, recent work has demonstrated that the replicating longbeachae-LCV is decorated with the ER protein calnexin (16). This indicates that these pathogens may indeed develop similar replicative niches inside eukaryotic cells, albeit through different mechanisms.…”

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confidence: 99%

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Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires

et al. 2015

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Legionella organisms are environmental bacteria and accidental human pathogens that can cause severe pneumonia, termed Legionnaires' disease. These bacteria replicate within a pathogen-derived vacuole termed the Legionella-containing vacuole (LCV). Our understanding of the development and dynamics of this vacuole is based on extensive analysis of Legionella pneumophila. Here, we have characterized the Legionella longbeachae replicative vacuole (longbeachae-LCV) and demonstrated that, despite important genomic differences, key features of the replicative LCV are comparable to those of the LCV of L. pneumophila (pneumophila-LCV). We constructed a Dot/Icm-deficient strain by deleting dotB and demonstrated the inability of this mutant to replicate inside THP-1 cells. L. longbeachae does not enter THP-1 cells as efficiently as L. pneumophila, and this is reflected in the observation that translocation of BlaM-RalF LLO (where RalF LLO is the L. longbeachae homologue of RalF) into THP-1 cells by the L. longbeachae Dot/Icm system is less efficient than that by L. pneumophila. This difference is negated in A549 cells where L. longbeachae and L. pneumophila infect with similar entry dynamics. A ␤-lactamase assay was employed to demonstrate the translocation of a novel family of proteins, the Rab-like effector (Rle) proteins. Immunofluorescence analysis confirmed that these proteins enter the host cell during infection and display distinct subcellular localizations, with RleA and RleC present on the longbeachae-LCV. We observed that the host Rab GTPase, Rab1, and the v-SNARE Sec22b are also recruited to the longbeachae-LCV during the early stages of infection, coinciding with the LCV avoiding endocytic maturation. These studies further our understanding of the L. longbeachae replicative vacuole, highlighting phenotypic similarities to the vacuole of L. pneumophila as well as unique aspects of LCV biology. L egionella species are environmental bacteria that replicate within a unique vacuole in a range of protozoan hosts. For particular species of Legionella, this capacity for intracellular replication contributes to their pathogenic capacity. Upon human inhalation of contaminated aerosols, Legionella can enter the lungs and infect alveolar macrophages, leading to a severe pneumonia termed Legionnaires' disease. Legionella pneumophila and Legionella longbeachae are the primary causative agents of Legionnaires' disease. L. pneumophila is responsible for up to 90% of Legionnaires' disease in Europe and the United States, and L. longbeachae accounts for approximately 50% of cases in Australia and New Zealand (1, 2). Interestingly, in recent years there has been a global increase in the detection and incidence of infection caused by L. longbeachae (3, 4).Despite causing clinically indistinguishable infections, L. longbeachae and L. pneumophila have distinct environmental niches. L. pneumophila is an aquatic organism, found in both natural and human-made aquatic environments, and L. longbeachae is predominantly found in soil envi...

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Section: Resultssupporting

confidence: 51%

Section: Figmentioning

confidence: 60%

mentioning

confidence: 99%

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Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires

et al. 2015

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“…Some L. pneumophila Icm/Dot substrates target and subvert pivotal regulators of eukaryotic signal transduction and vesicle trafficking, such as small GTPases (8 -13) or phosphoinositide (PI) lipids (14 -16). Several Legionella effectors anchor to the LCV membrane by specifically binding to the phosphorylated phosphatidylinositol (PtdIns) headgroup of PI lipids, namely PtdIns(4)P (17)(18)(19)(20)(21)(22) and PtdIns(3)P (23)(24)(25), which are implicated in secretory and endosomal vesicle trafficking, respectively. Moreover, L. pneumophila produces two non-homologous Icm/Dot-translocated PI 3-phosphatases, SidF and SidP, which might modulate the LCV PI pattern (26,27).…”

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confidence: 99%

A Type IV Translocated Legionella Cysteine Phytase Counteracts Intracellular Growth Restriction by Phytate

Weber

Stirnimann

Wieser

et al. 2014

Journal of Biological Chemistry

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Background: Legionella governs pathogen-host interactions by translocating ϳ300 "effector" proteins through a type IV secretion system. Results: The hitherto unrecognized effector LppA is a phytase that counteracts intracellular bacterial growth restriction by phytate. Conclusion:The chelator phytate is a bacteriostatic component of cell-autonomous immunity, which is degraded by a bacterial effector. Significance: Legionella LppA represents the first translocated phytase and a potential therapeutic target.

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“…SidC and SdcA were previously implicated in ER acquisition to the LCV of L. pneumophila and L. longbeachae (Weber et al 2006;Ragaz et al 2008;Dolinsky et al 2014). Recent determination of the crystal structure of SidC led to the discovery that SidC and SdcA belong to a new family of E3 ubiquitin ligases, which transfer ubiquitin from several ubiquitin conjugating E2 enzymes onto protein targets (Hsu et al 2014).…”

Section: Additional Effectors With Important Roles In Lcv Maturationmentioning

confidence: 99%

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

Mattheis

Tate

et al. 2015

Can. J. Microbiol.

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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.

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The Legionella longbeachae Icm/Dot Substrate SidC Selectively Binds Phosphatidylinositol 4-Phosphate with Nanomolar Affinity and Promotes Pathogen Vacuole-Endoplasmic Reticulum Interactions

Cited by 54 publications

References 63 publications

Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires

Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires

A Type IV Translocated Legionella Cysteine Phytase Counteracts Intracellular Growth Restriction by Phytate

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

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