The LysR-type transcriptional regulator LelA co-regulates various effectors in different Legionella species.

The intracellular pathogen Legionella pneumophila translocates more than 300 effector proteins into its host cells. The expression levels of the genes encoding these effectors are orchestrated by an intricate regulatory network. Here, we introduce LelA, the first L.

The genus core effectors display functional conservation among orthologs by themselves or combined with an accessory protein.

The intracellular pathogen as well as other species, utilize the Icm/Dot type-IV secretion system to translocate an exceptionally large and diverse repertoire of effectors into their host cells. However, only nine core effectors were found to be present in all analyzed species. In this study, we investigated the core effectors, and used intracellular growth complementation to determine whether orthologs of core effectors perform the same function in different species.

A horizontally acquired Legionella genomic island encoding a LuxR type regulator and effector proteins displays variation in gene content and regulation.

The intracellular pathogen Legionella pneumophila translocates >300 effector proteins into host cells, many of which are regulated at the transcriptional level. Here, we describe a novel L. pneumophila genomic island, which undergoes horizontal gene transfer within the Legionella genus.

A Novel Genomic Island Encodes a Copper-Responsive Regulatory System and a Single Icm/Dot Effector Protein Transcriptionally Activated by Copper.

The intracellular pathogen utilizes the Icm/Dot type IV secretion system to translocate >300 effector proteins into host cells during infection. The regulation of some of these effector-encoding genes was previously shown to be coordinated by several global regulators, including three two-component systems (TCSs) found in all the species examined. Here, we describe the first genomic island encoding a single Icm/Dot effector and a dedicated TCS, which regulates its expression.

Study of Effector Domains Revealed Novel and Prevalent Phosphatidylinositol 3-Phosphate Binding Domains.

and other species replicate intracellularly using the Icm/Dot type IV secretion system. In this system translocates >300 effectors into host cells and in the genus thousands of effectors were identified, the function of most of which is unknown. Fourteen effectors were previously shown to specifically bind phosphoinositides (PIs) using dedicated domains.

The emergency department length of stay: Is the time running out?

Purpose: To examine the relationships between emergency department length of stay (EDLOS) with hospital length of stay (HLOS) and clinical outcome in hemodynamically stable trauma patients.

Methods: Prospective data collected for 2 years from consecutive trauma patients admitted to the trauma resuscitation bay. Only stable blunt trauma patients with appropriate trauma triage criteria requiring trauma team activation were included in the study.

The single-domain response regulator LerC functions as a connector protein in the Legionella pneumophila effectors regulatory network.

The intracellular pathogen Legionella pneumophila translocates more than 300 effector proteins into host cells during infection. The PmrAB two-component system (TCS) has been shown to activate the expression of a large pool of these effector-encoding genes (EEGs) and the LetAS TCS, as part of the LetAS-RsmYZ-CsrA cascade, has been shown to repress the expression of another pool of EEGs. We identified a single-domain response regulator (SDRR), named LerC, which functions as a connector protein between the PmrAB and the LetAS TCSs.

The Legionella pneumophila Incomplete Phosphotransferase System Is Required for Optimal Intracellular Growth and Maximal Expression of PmrA-Regulated Effectors.

The nitrogen phosphotransferase system (PTS) is a regulatory cascade present in many bacteria, where it controls different functions. This system is usually composed of three basic components: enzyme I (EI), NPr, and EIIA (encoded by the , , and genes, respectively). In , as well as in many other species, the EIIA component is missing.

Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires.

Infection by the human pathogen Legionella pneumophila relies on the translocation of ∼ 300 virulence proteins, termed effectors, which manipulate host cell processes. However, almost no information exists regarding effectors in other Legionella pathogens. Here we sequenced, assembled and characterized the genomes of 38 Legionella species and predicted their effector repertoires using a previously validated machine learning approach.

The Legionella pneumophila CpxRA two-component regulatory system: new insights into CpxR's function as a dual regulator and its connection to the effectors regulatory network.

Legionella pneumophila utilizes the Icm/Dot type-IV secretion system to translocate approximately 300 effector proteins into host cells, and the CpxRA two-component system (TCS) was previously shown to regulate the expression of several of these effectors. In this study, we expanded the pool of L. pneumophila CpxR-regulated genes to 38, including 27 effector-encoding genes.

Two Fis regulators directly repress the expression of numerous effector-encoding genes in Legionella pneumophila.

Legionella pneumophila is an intracellular human pathogen that utilizes the Icm/Dot type IVB secretion system to translocate a large repertoire of effectors into host cells. For most of these effectors, there is no information regarding their regulation. Therefore, the aim of this study was to examine the involvement of the three L.

Identification of novel Coxiella burnetii Icm/Dot effectors and genetic analysis of their involvement in modulating a mitogen-activated protein kinase pathway.

Coxiella burnetii, the causative agent of Q fever, is a human intracellular pathogen that utilizes the Icm/Dot type IVB secretion system to translocate effector proteins into host cells. To identify novel C. burnetii effectors, we applied a machine-learning approach to predict C.

Identification of Legionella pneumophila effectors regulated by the LetAS-RsmYZ-CsrA regulatory cascade, many of which modulate vesicular trafficking.

Legionella pneumophila, the causative agent of Legionnaires' disease, is an intracellular human pathogen that utilizes the Icm/Dot type IVB secretion system to translocate a large repertoire of effectors into host cells. To find coregulated effectors, we performed a bioinformatic genomic screen with the aim of identifying effector-encoding genes containing putative CsrA regulatory elements. The regulation of these genes by the LetAS-RsmYZ-CsrA regulatory cascade was experimentally validated by examining their levels of expression in deletion mutants of relevant regulators and by site-directed mutagenesis of the putative CsrA sites.

The Legionella pneumophila two-component regulatory systems that participate in the regulation of Icm/Dot effectors.

Legionella pneumophila, the causative agent of Legionnaires' disease, actively manipulates intracellular processes to establish a replication niche inside their host cells. The establishment of its replication niche requires a functional Icm/Dot type IV secretion system which translocates about 300 effector proteins into the host cells during infection. This enormous number of effectors should be coordinated at the level of gene expression, in order to be expressed and translocated at the correct time and appropriate amounts.

Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal.

Legionella and Coxiella are intracellular pathogens that use the virulence-related Icm/Dot type-IVB secretion system to translocate effector proteins into host cells during infection. These effectors were previously shown to contain a C-terminal secretion signal required for their translocation. In this research, we implemented a hidden semi-Markov model to characterize the amino acid composition of the signal, thus providing a comprehensive computational model for the secretion signal.

Identification of legionella effectors using bioinformatic approaches.

Legionella pneumophila the causative agent of Legionnaires' disease, actively manipulates host cell processes to establish a replication niche inside host cells. The establishment of its replication niche requires a functional Icm/Dot type IV secretion system which translocates about 300 effector proteins into host cells during infection. Many of these effectors were first identified as effector candidates by several bioinformatic approaches, and these predicted effectors were later examined experimentally for translocation and a large number of which were validated as effector proteins.

Identification of two Legionella pneumophila effectors that manipulate host phospholipids biosynthesis.

The intracellular pathogen Legionella pneumophila translocates a large number of effector proteins into host cells via the Icm/Dot type-IVB secretion system. Some of these effectors were shown to cause lethal effect on yeast growth. Here we characterized one such effector (LecE) and identified yeast suppressors that reduced its lethal effect.

Molecular mechanism of elongation factor 1A inhibition by a Legionella pneumophila glycosyltransferase.

Legionnaires' disease is caused by a lethal colonization of alveolar macrophages with the Gram-negative bacterium Legionella pneumophila. LpGT (L. pneumophila glucosyltransferase; also known as Lgt1) has recently been identified as a virulence factor, shutting down protein synthesis in the human cell by specific glucosylation of EF1A (elongation factor 1A), using an unknown mode of substrate recognition and a retaining mechanism for glycosyl transfer.

Genome-scale identification of Legionella pneumophila effectors using a machine learning approach.

A large number of highly pathogenic bacteria utilize secretion systems to translocate effector proteins into host cells. Using these effectors, the bacteria subvert host cell processes during infection. Legionella pneumophila translocates effectors via the Icm/Dot type-IV secretion system and to date, approximately 100 effectors have been identified by various experimental and computational techniques.