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Molecular Cell Jan 2020The family of bacterial SidE enzymes catalyzes non-canonical phosphoribosyl-linked (PR) serine ubiquitination and promotes infectivity of Legionella pneumophila. Here,...
The family of bacterial SidE enzymes catalyzes non-canonical phosphoribosyl-linked (PR) serine ubiquitination and promotes infectivity of Legionella pneumophila. Here, we describe identification of two bacterial effectors that reverse PR ubiquitination and are thus named deubiquitinases for PR ubiquitination (DUPs; DupA and DupB). Structural analyses revealed that DupA and SidE ubiquitin ligases harbor a highly homologous catalytic phosphodiesterase (PDE) domain. However, unlike SidE ubiquitin ligases, DupA displays increased affinity to PR-ubiquitinated substrates, which allows DupA to cleave PR ubiquitin from substrates. Interfering with DupA-ubiquitin binding switches its activity toward SidE-type ligase. Given the high affinity of DupA to PR-ubiquitinated substrates, we exploited a catalytically inactive DupA mutant to trap and identify more than 180 PR-ubiquitinated host proteins in Legionella-infected cells. Proteins involved in endoplasmic reticulum (ER) fragmentation and membrane recruitment to Legionella-containing vacuoles (LCV) emerged as major SidE targets. The global map of PR-ubiquitinated substrates provides critical insights into host-pathogen interactions during Legionella infection.
Topics: A549 Cells; Bacterial Proteins; Catalytic Domain; Cell Line; Cell Line, Tumor; Deubiquitinating Enzymes; Endoplasmic Reticulum; HEK293 Cells; HeLa Cells; Host-Pathogen Interactions; Humans; Legionella pneumophila; Legionnaires' Disease; Serine; Ubiquitin; Ubiquitination; Vacuoles
PubMed: 31732457
DOI: 10.1016/j.molcel.2019.10.019 -
Epidemiology and Infection Jul 2023Over the past two decades, the incidence of legionellosis has been steadily increasing in the United States though there is noclear explanation for the main factors... (Review)
Review
Over the past two decades, the incidence of legionellosis has been steadily increasing in the United States though there is noclear explanation for the main factors driving the increase. While legionellosis is the leading cause of waterborne outbreaks in the US, most cases are sporadic and acquired in community settings where the environmental source is never identified. This scoping review aimed to summarise the drivers of infections in the USA and determine the magnitude of impact each potential driver may have. A total of 1,738 titles were screened, and 18 articles were identified that met the inclusion criteria. Strong evidence was found for precipitation as a major driver, and both temperature and relative humidity were found to be moderate drivers of incidence. Increased testing and improved diagnostic methods were classified as moderate drivers, and the ageing U.S. population was a minor driver of increasing incidence. Racial and socioeconomic inequities and water and housing infrastructure were found to be potential factors explaining the increasing incidence though they were largely understudied in the context of non-outbreak cases. Understanding the complex relationships between environmental, infrastructure, and population factors driving legionellosis incidence is important to optimise mitigation strategies and public policy.
Topics: United States; Humans; Incidence; Legionellosis; Disease Outbreaks; Temperature; Legionnaires' Disease
PubMed: 37503568
DOI: 10.1017/S0950268823001206 -
JAAPA : Official Journal of the... Oct 2022Legionnaires disease is an important, relatively uncommon, yet well known form of atypical community-acquired pneumonia (CAP). If not appropriately treated in the early... (Review)
Review
Legionnaires disease is an important, relatively uncommon, yet well known form of atypical community-acquired pneumonia (CAP). If not appropriately treated in the early stage of infection, it can be fatal. Several factors increase the risk of contracting Legionnaires disease, including age over 50 years, chronic cardiovascular disease, underlying respiratory disease, chronic renal disease, diabetes, smoking, any immunosuppressing condition, travel history, and certain types of employment. Legionnaires disease can present without the usual symptoms associated with pneumonia. The incidence of Legionnaires disease is increasing, and because of its morbidity and mortality, clinicians should consider it in the differential when treating patients with CAP. This article reviews the pathophysiology and treatment of Legionnaires disease and when to refer patients to tertiary centers for higher levels of care, including extracorporeal membrane oxygenation.
Topics: Community-Acquired Infections; Extracorporeal Membrane Oxygenation; Humans; Legionella; Legionnaires' Disease; Middle Aged; Pneumonia
PubMed: 36165547
DOI: 10.1097/01.JAA.0000873792.00538.78 -
Frontiers in Immunology 2020is the causative agent of a severe pneumonia called Legionnaires' disease. The environmental bacterium replicates in free-living amoebae as well as in lung macrophages... (Review)
Review
is the causative agent of a severe pneumonia called Legionnaires' disease. The environmental bacterium replicates in free-living amoebae as well as in lung macrophages in a distinct compartment, the -containing vacuole (LCV). The LCV communicates with a number of cellular vesicle trafficking pathways and is formed by a plethora of secreted bacterial effector proteins, which target host cell proteins and lipids. Phosphoinositide (PI) lipids are pivotal determinants of organelle identity, membrane dynamics and vesicle trafficking. Accordingly, eukaryotic cells tightly regulate the production, turnover, interconversion, and localization of PI lipids. modulates the PI pattern in infected cells for its own benefit by (i) recruiting PI-decorated vesicles, (ii) producing effectors acting as PI interactors, phosphatases, kinases or phospholipases, and (iii) subverting host PI metabolizing enzymes. The PI conversion from PtdIns(3) to PtdIns(4) represents a decisive step during LCV maturation. In this review, we summarize recent progress on elucidating the strategies, by which subverts host PI lipids to promote LCV formation and intracellular replication.
Topics: Bacterial Proteins; Cell Membrane; Endoplasmic Reticulum; Host-Pathogen Interactions; Humans; Legionella pneumophila; Legionnaires' Disease; Macrophages; Phosphatidylinositols; Secretory Vesicles; Transport Vesicles; Vacuoles
PubMed: 32117224
DOI: 10.3389/fimmu.2020.00025 -
Praxis 2020CME: Legionella pneumonia Legionnaire's disease is a usually severe form of pneumonia caused by Legionella pneumophila, a Gram-negative bacterium with an airborne...
CME: Legionella pneumonia Legionnaire's disease is a usually severe form of pneumonia caused by Legionella pneumophila, a Gram-negative bacterium with an airborne transmission. The infection is acquired in the community, but cases of hospital acquisition from hot water systems have been described. The most common clinical features are cough, fever, gastrointestinal symptoms, hyponatremia and altered liver function tests. The mainstay investigations to confirm diagnosis are urine antigen, sputum polymerase chain reaction, sputum or bronchial alveolar lavage cultures. Standard antibiotic treatment are macrolides or fluoroquinolones.
Topics: Anti-Bacterial Agents; Humans; Legionella pneumophila; Legionnaires' Disease; Pneumonia; Polymerase Chain Reaction
PubMed: 32517597
DOI: 10.1024/1661-8157/a003467 -
Current Issues in Molecular Biology 2021Legionnaires' disease and Pontiac fever are both diseases with important public health implications and require prompt and thorough responses to outbreaks for future...
Legionnaires' disease and Pontiac fever are both diseases with important public health implications and require prompt and thorough responses to outbreaks for future prevention. Effective methods for defining, diagnosing, reporting and responding to legionellosis outbreaks ideally should be standardized across countries. Therefore, the European Union surveillance methods for countering Legionnaires' disease is a useful model especially for travel-associated Legionnaires' disease (TALD) cases which are on the rise. Multi-country surveillance in the EU and European Economic Area (EEA) has evolved since the first organizational efforts in the 1980's to the currently responsible, European Legionnaires' Disease Surveillance Network (ELDSNet). This chapter outlines the practices of the EU surveillance of Legionnaires' disease including their schemata, definitions, responsibilities of participating members, methods and the results of the data collected since the program's inception. Lastly, improvements must still be made as the incidence of Legionnaires' disease in the EU is likely underestimated due to underreporting and/or underdiagnosis. Nearly 70% of cases are reported from only four countries, France, Germany, Italy and Spain, which represent 50% of the EU population.
Topics: Disease Outbreaks; Europe; Humans; Legionella; Legionnaires' Disease; Public Health Surveillance
PubMed: 33284133
DOI: 10.21775/cimb.042.081 -
The New England Journal of Medicine Dec 2021
Topics: Diagnosis, Differential; Female; Humans; Legionella pneumophila; Legionnaires' Disease; Lung; Middle Aged; Radiography, Thoracic
PubMed: 34874634
DOI: 10.1056/NEJMcps2108991 -
Biomedica : Revista Del Instituto... Mar 2021Introduction: Legionellosis is a bacterial respiratory disease with an environmental origin in the community or in hospitals; it is usually associated with devices,...
Introduction: Legionellosis is a bacterial respiratory disease with an environmental origin in the community or in hospitals; it is usually associated with devices, facilities, and buildings. The most common clinical form is the pneumonic, known as legionnaires’ disease. Objective: To determine the evolution of legionellosis cases in Spain from 2010 to 2015. Materials and methods: This was a descriptive study of time series with an analysis of the legionellosis cases notified to the Centro Nacional de Epidemiología (Government of Spain). Case distribution was determined according to sex, the autonomous community of origin, month, and age groups differentiating in the latter between men and women. Results: Case count in men was more than double compared to that in women. The cases notified by nine of the autonomous communities showed an increase at the end of the period, especially in Castilla y León, Navarra, and the Basque Country but also notable in Castilla-La Mancha. A seasonal pattern was identified with an epidemic peak in July-September and a greater number of cases among 50-years old people from both sexes. Conclusion: Despite its low prevalence compared to other respiratory diseases, legionellosis has a great impact on public health. Its distribution in Spain is global and heterogeneous with cases increasing in the last two years. Therefore, better disease prevention and control measures are recommended.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Infant; Legionellosis; Male; Middle Aged; Spain; Time Factors; Young Adult
PubMed: 33761200
DOI: 10.7705/biomedica.5367 -
International Journal of Molecular... Feb 2021are Gram-stain-negative rods associated with water environments: either natural or man-made systems. The inhalation of aerosols containing bacteria leads to the... (Review)
Review
are Gram-stain-negative rods associated with water environments: either natural or man-made systems. The inhalation of aerosols containing bacteria leads to the development of a severe pneumonia termed Legionnaires' disease. To establish an infection, these bacteria adapt to growth in the hostile environment of the host through the unusual structures of macromolecules that build the cell surface. The outer membrane of the cell envelope is a lipid bilayer with an asymmetric composition mostly of phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet. The major membrane-forming phospholipid of spp. is phosphatidylcholine (PC)-a typical eukaryotic glycerophospholipid. PC synthesis in cells occurs via two independent pathways: the -methylation (Pmt) pathway and the Pcs pathway. The utilisation of exogenous choline by spp. leads to changes in the composition of lipids and proteins, which influences the physicochemical properties of the cell surface. This phenotypic plasticity of the cell envelope determines the mode of interaction with the macrophages, which results in a decrease in the production of proinflammatory cytokines and modulates the interaction with antimicrobial peptides and proteins. The surface-exposed O-chain of sg1 LPS consisting of a homopolymer of 5-acetamidino-7-acetamido-8-O-acetyl-3,5,7,9-tetradeoxy-l-glycero-d-galacto-non-2-ulosonic acid is probably the first component in contact with the host cell that anchors the bacteria in the host membrane. Unusual in terms of the structure and function of individual LPS regions, it makes an important contribution to the antigenicity and pathogenicity of bacteria.
Topics: Antigens, Bacterial; Bacterial Proteins; Choline; Fatty Acids; Genes, Bacterial; Genetic Variation; Host-Pathogen Interactions; Humans; Legionella; Lipopolysaccharides; Membrane Lipids; Phosphatidylcholines; Phospholipids; Species Specificity
PubMed: 33540788
DOI: 10.3390/ijms22031487