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Annual Review of Pathology Jan 2020species are environmental gram-negative bacteria able to cause a severe form of pneumonia in humans known as Legionnaires' disease. Since the identification of in... (Review)
Review
species are environmental gram-negative bacteria able to cause a severe form of pneumonia in humans known as Legionnaires' disease. Since the identification of in 1977, four decades of research on biology and Legionnaires' disease have brought important insights into the biology of the bacteria and the molecular mechanisms that these intracellular pathogens use to cause disease in humans. Nowadays, species constitute a remarkable model of bacterial adaptation, with a genus genome shaped by their close coevolution with amoebae and an ability to exploit many hosts and signaling pathways through the secretion of a myriad of effector proteins, many of which have a eukaryotic origin. This review aims to discuss current knowledge of infection mechanisms and future research directions to be taken that might answer the many remaining open questions. This research will without a doubt be a terrific scientific journey worth taking.
Topics: Adaptation, Physiological; Amoeba; Eukaryotic Cells; Host-Pathogen Interactions; Humans; Legionella; Legionella pneumophila; Legionnaires' Disease
PubMed: 31657966
DOI: 10.1146/annurev-pathmechdis-012419-032742 -
Infectious Disease Clinics of North... Mar 2017Severe legionella pneumonia poses a diagnostic challenge and requires early intervention. Legionnaire's disease can have several presenting signs, symptoms, and... (Review)
Review
Severe legionella pneumonia poses a diagnostic challenge and requires early intervention. Legionnaire's disease can have several presenting signs, symptoms, and laboratory abnormalities that suggest that Legionella pneumophila is the pathogen, but none of these are sufficient to distinguish L pneumophila pneumonia from other respiratory pathogens. L pneumophila is primarily an intracellular pathogen and needs treatment with antibiotics that efficiently enter the intracellular space.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Diagnosis, Differential; Humans; Legionella pneumophila; Legionnaires' Disease; Pneumonia
PubMed: 28159171
DOI: 10.1016/j.idc.2016.10.009 -
Journal of Molecular Cell Biology Nov 2023Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease.... (Review)
Review
Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease. During infections, L. pneumophila releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the host. Notably, certain effector proteins mediate posttranslational modifications (PTMs), serving as useful approaches exploited by L. pneumophila to modify host proteins. Some effectors catalyze the addition of host protein PTMs, while others mediate the removal of PTMs from host proteins. In this review, we summarize L. pneumophila effector-mediated PTMs of host proteins, including phosphorylation, ubiquitination, glycosylation, AMPylation, phosphocholination, methylation, and ADP-ribosylation, as well as dephosphorylation, deubiquitination, deAMPylation, deADP-ribosylation, dephosphocholination, and delipidation. We describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.
Topics: Humans; Legionella pneumophila; Legionnaires' Disease; Protein Processing, Post-Translational; Vacuoles; Ubiquitination
PubMed: 37156500
DOI: 10.1093/jmcb/mjad032 -
JAMA Internal Medicine Dec 2014The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial.
OBJECTIVE
To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia.
DESIGN, SETTING, AND PARTICIPANTS
Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation.
INTERVENTIONS
Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm.
MAIN OUTCOMES AND MEASURES
Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90 mm Hg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7.
RESULTS
After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6% difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95% CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95% CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95% CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95% CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9% vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms.
CONCLUSIONS AND RELEVANCE
We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00818610.
Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Community-Acquired Infections; Drug Therapy, Combination; Follow-Up Studies; Hospitalization; Humans; Legionella pneumophila; Legionnaires' Disease; Macrolides; Middle Aged; Odds Ratio; Pneumonia, Bacterial; Severity of Illness Index; Switzerland; Treatment Outcome; beta-Lactams
PubMed: 25286173
DOI: 10.1001/jamainternmed.2014.4887 -
Seminars in Cell & Developmental Biology Dec 2022Legionella pneumophila, a Gram-negative intracellular bacterium, is one of the major causes of Legionnaires' disease, a specific type of atypical pneumonia. Despite... (Review)
Review
Legionella pneumophila, a Gram-negative intracellular bacterium, is one of the major causes of Legionnaires' disease, a specific type of atypical pneumonia. Despite intensive research efforts that elucidated many relevant structural, molecular and medical insights into Legionella's pathogenicity, Legionnaires' disease continues to present an ongoing public health concern. Legionella's virulence is based on its ability to simultaneously hijack multiple molecular pathways of the host cell to ensure its fast replication and dissemination. Legionella usurps the host ubiquitin system through multiple effector proteins, using the advantage of both conventional and unconventional (phosphoribosyl-linked) ubiquitination, thus providing optimal conditions for its replication. In this review, we summarize the current understanding of L. pneumophila from medical, biochemical and molecular perspectives. We describe the clinical disease presentation, its diagnostics and treatment, as well as host-pathogen interactions, with the emphasis on the ability of Legionella to target the host ubiquitin system upon infection. Furthermore, the interdisciplinary use of innovative technologies enables better insights into the pathogenesis of Legionnaires' disease and provides new opportunities for its treatment and prevention.
Topics: Humans; Bacterial Proteins; Host-Pathogen Interactions; Legionella pneumophila; Legionnaires' Disease; Ubiquitin
PubMed: 35177348
DOI: 10.1016/j.semcdb.2022.02.008 -
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 -
Przeglad Epidemiologiczny 2018The aim of the study was to assess the epidemiological situation of legionellosis in Poland in 2016 in comparison to the preceding years.
OBJECTIVE
The aim of the study was to assess the epidemiological situation of legionellosis in Poland in 2016 in comparison to the preceding years.
MATERIAL AND METHODS
The assessment was based on national surveillance data published in the annual bulletin: “Infectious diseases and poisonings in Poland in 2016” and its prior versions along with data from legionellosis case reports sent from Sanitary-Epidemiological Stations to the Department of Epidemiology of NIPH - NIH.
RESULTS
In Poland, both two main forms of legionellosis - Legionnaires’ disease and Pontiac fever are routinely reported to the surveillance system. In 2016, a total of 27 cases of legionellosis were registered, including 25 cases of Legionnaires’ disease and 2 cases of Pontiac fever; in 2016, a total of 27 cases of legionellosis have been reported, including 25 cases of Legionnaires’ disease and 2 cases of Pontiac fever; the annual incidence rate 0.070 (per 100,000 population) was comparable to previous year (0.060) but almost twice as high as the median (incidence) for 2010-2014. The infections were reported in 11 provinces, including two, which in previous years usually did not register any cases; only two provinces (out of 16 in the country) have reported no cases in recent years. The incidence in men (0.080 per 100,000) was higher compared to women (0.055). All reported cases were sporadic and, except for one mild case of Legionnaires’ disease, required hospitalization. The Sanitary Inspection reported two fatal cases – both women aged 59 and 69. Twenty cases were autochthonous including four cases linked with contaminated water systems in hospitals. Seven cases were associated with travel abroad (to Germany, Russia, Greece, Australia, USA and Thailand).
SUMMARY AND CONCLUSIONS
Despite the increase in the number of cases in recent years as well as number of provinces, which detected cases, the annual incidence of legionellosis in Poland remains one of the lowest in the EU, which suggests that this infection is likely under-recognized and underdiagnosed in all provinces of the country.
Topics: Adolescent; Adult; Aged; Female; Humans; Incidence; Legionellosis; Male; Middle Aged; Poland; Registries; Young Adult
PubMed: 30111084
DOI: No ID Found -
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 -
Przeglad Epidemiologiczny 2019The aim of this study is to assess the epidemiological situation of legionellosis in Poland in 2017 in comparison with previous years.
OBJECTIVE
The aim of this study is to assess the epidemiological situation of legionellosis in Poland in 2017 in comparison with previous years.
MATERIAL AND METHODS
The analysis is based on national surveillance data published in the annual bulletin: “Infectious diseases and poisonings in Poland in 2017” and bulletins from previous years along with data from legionellosis case reports collected and sent to the Department of Epidemiology of Infectious Diseases and Surveillance NIPH – NIH by Sanitary and Epidemiological Stations.
RESULTS
In Poland, both cases of Legionnaires’ disease (an acute form of infection with pneumonia) and Pontiac fever (a mild, influenza-like form of infection) are routinely reported to the surveillance system. In 2017, a total of 39 cases of legionellosis were registered, including 38 cases of Legionnaires’ disease and 1 case of Pontiac fever; the annual incidence rate 0.102 (per 100,000 population) has increased by almost 50 percent since previous year (0.070) and is almost three times higher than the median incidence (0.036) for 2011-2015. The infections were reported in fourteen voivodeships; only one voivodeship (Świętokrzyskie) did not register any case in last years. The incidence in men (0.129 per 100,000) was higher compared to women (0.076); the highest incidence (0.323) was noted in men aged 50-59. All reported cases were sporadic and were hospitalised. The Sanitary Inspection reported nine fatal cases – 6 women and 3 men. Thirty three cases were autochthonous including four cases linked with contaminated water systems in health-care settings. Six cases were associated with travels abroad (to Egypt, Albania, Italy and Crete).
SUMMARY AND CONCLUSIONS
Although in recent years number of reported cases continues to rise, the incidence of legionellosis in Poland remains one of the lowest in the entire EU. Also draws attention variation of incidence between provinces and a high mortality among reported cases. Our data suggest significant under-diagnosis of legionellosis. A priority remains to improve early diagnosis of Legionnaires’ disease in health care settings.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Incidence; Legionellosis; Legionnaires' Disease; Male; Middle Aged; Poland; Registries; Young Adult
PubMed: 31385671
DOI: 10.32394/pe.73.26