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The Journal of Biological Chemistry Dec 2023Legionella pneumophila is an environmental bacterium, which replicates in amoeba but also in macrophages, and causes a life-threatening pneumonia called Legionnaires'...
Legionella pneumophila is an environmental bacterium, which replicates in amoeba but also in macrophages, and causes a life-threatening pneumonia called Legionnaires' disease. The opportunistic pathogen employs the α-hydroxy-ketone compound Legionella autoinducer-1 (LAI-1) for intraspecies and interkingdom signaling. LAI-1 is produced by the autoinducer synthase Legionella quorum sensing A (LqsA), but it is not known, how LAI-1 is released by the pathogen. Here, we use a Vibrio cholerae luminescence reporter strain and liquid chromatography-tandem mass spectrometry to detect bacteria-produced and synthetic LAI-1. Ectopic production of LqsA in Escherichia coli generated LAI-1, which partitions to outer membrane vesicles (OMVs) and increases OMV size. These E. coli OMVs trigger luminescence of the V. cholerae reporter strain and inhibit the migration of Dictyostelium discoideum amoeba. Overexpression of lqsA in L.pneumophila under the control of strong stationary phase promoters (P or P), but not under control of its endogenous promoter (P), produces LAI-1, which is detected in purified OMVs. These L. pneumophila OMVs trigger luminescence of the Vibrio reporter strain and inhibit D. discoideum migration. L. pneumophila OMVs are smaller upon overexpression of lqsA or upon addition of LAI-1 to growing bacteria, and therefore, LqsA affects OMV production. The overexpression of lqsA but not a catalytically inactive mutant promotes intracellular replication of L. pneumophila in macrophages, indicating that intracellularly produced LA1-1 modulates the interaction in favor of the pathogen. Taken together, we provide evidence that L. pneumophila LAI-1 is secreted through OMVs and promotes interbacterial communication and interactions with eukaryotic host cells.
Topics: Humans; Bacterial Proteins; Dictyostelium; Escherichia coli; Legionella; Legionella pneumophila; Legionnaires' Disease; Quorum Sensing
PubMed: 37866633
DOI: 10.1016/j.jbc.2023.105376 -
Microbiology Spectrum Jun 2022The distribution of pathogenic in the environmental soil and water of China has not been documented yet. In this study, was detected in 129 of 575 water (22.43%) and...
The distribution of pathogenic in the environmental soil and water of China has not been documented yet. In this study, was detected in 129 of 575 water (22.43%) and 41 of 442 soil samples (9.28%) by culture. Twelve species were identified, of which 11 were disease-associated. Of the -positive samples, 109 of 129 (84.50%) water and 29 of 41 (70.73%) soil were positive for L. pneumophila, which accounted for about 75% of isolates in both water and soil, suggesting L. pneumophila was the most frequent species. Soil showed a higher diversity of spp. as compared with water (0.6279 versus 0.4493). In contrast, serogroup (sg) 1 was more prevalent among L. pneumophila isolates from water than from soil (26.66% versus 12.21%). Moreover, many disease-associated sequence types (STs) of L. pneumophila were found in China. Intragenic recombination was acting on L. pneumophila from both water and soil. Phylogeny, population structure, and molecular evolution analyses revealed a probable existence of L. pneumophila isolates with a special genetic background that is more adaptable to soil or water sources and a small proportion of genetic difference between water and soil isolates. The detection of viable, clinically relevant demonstrates soil as another source for harboring and dissemination of pathogenic bacteria in China. Future research should assess the implication in public health with the presence of in the soil and illustrate the genetic and pathogenicity difference of between water and soil, particularly the most prevalent L. pneumophila. Pathogenic spp. is the causative agent of Legionnaires' disease (LD), and L. pneumophila is the most common one. Most studies have focused on L. pneumophila from water and clinical samples. However, the soil is another important reservoir for this bacterium, and the distribution of spp. in water and soil sources has not been compared and documented in China yet. Discovering the distribution of spp. and L. pneumophila in the two environments may help a deep understanding of the pathogenesis and molecular evolution of the bacterium. Our research systematically uncovered the distributions of spp. in different regions and sources (e.g., water and soil) of China. Moreover, phylogeny, population structure, and molecular evolution study revealed the possible existence of L. pneumophila with a special genetic background that is more adaptable to soil or water sources, and genetic difference may exist.
Topics: Humans; Legionella; Legionella pneumophila; Legionnaires' Disease; Soil; Water; Water Microbiology
PubMed: 35438512
DOI: 10.1128/spectrum.01140-21 -
Euro Surveillance : Bulletin Europeen... Jul 2017Under the coordination of the European Centre for Disease Prevention and Control (ECDC), the European Legionnaires' disease Surveillance Network (ELDSNet) conducts...
Under the coordination of the European Centre for Disease Prevention and Control (ECDC), the European Legionnaires' disease Surveillance Network (ELDSNet) conducts surveillance of Legionnaires' disease (LD) in Europe. Between 2011 and 2015, 29 countries reported 30,532 LD cases to ECDC (28,188 (92.3%) confirmed and 2,344 (7.7%) probable). Four countries (France, Germany, Italy and Spain) accounted for 70.3% of all reported cases, although their combined populations represented only 49.9% of the study population. The age-standardised rate of all cases increased from 0.97 cases/100,000 population in 2011 to 1.30 cases/100,000 population in 2015, corresponding to an annual average increase of 0.09 cases/100,000 population (95%CI 0.02-0.14; p = 0.02). Demographics and infection setting remained unchanged with ca 70% of cases being community-acquired and 80% occurring in people aged 50 years and older. Clinical outcome was known for 23,164 cases, of whom 2,161 (9.3%) died. The overall case fatality ratio decreased steadily from 10.5% in 2011 to 8.1% in 2015, probably reflecting improved reporting completeness. Five countries (Austria, Czech Republic, Germany, Italy, and Norway) had increasing age-standardised LD notification rates over the 2011-15 period, but there was no increase in notification rates in countries where the 2011 rate was below 0.5/100,000 population.
Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Demography; Disease Notification; Disease Outbreaks; Europe; Female; Humans; Legionella pneumophila; Legionnaires' Disease; Male; Middle Aged; Population Surveillance; Seasons; Sex Distribution
PubMed: 28703097
DOI: 10.2807/1560-7917.ES.2017.22.27.30566 -
Journal of AOAC International Aug 2021Legionnaires' disease has been recognized since 1976 and Legionella pneumophila still accounts for more than 95% of cases. Approaches in countries, including France,... (Review)
Review
Legionnaires' disease has been recognized since 1976 and Legionella pneumophila still accounts for more than 95% of cases. Approaches in countries, including France, suggest that focusing risk reduction specifically on L. pneumophila is an effective strategy, as detecting L. pneumophila has advantages over targeting multiple species of Legionella. In terms of assays, the historically accepted plate culture method takes 10 days for confirmed Legionella spp. results, has variabilities which affect trending and comparisons, requires highly trained personnel to identify colonies on a plate in specialist laboratories, and does not recover viable-but-non-culturable bacteria. PCR is sensitive, specific, provides results in less than 24 h, and determines the presence/absence of Legionella spp. and/or L. pneumophila DNA. Whilst specialist personnel and laboratories are generally required, there are now on-site PCR options, but there is no agreement on comparing genome units to colony forming units and action limits. Immunomagnetic separation assays are culture-independent, detect multiple Legionella species, and results are available in 24 h, with automated processing options. Field-use lateral flow devices provide presence/absence determination of L. pneumophila serogroup 1 where sufficient cells are present, but testing potable waters is problematic. Liquid culture most probable number (MPN) assays provide confirmed L. pneumophila results in 7 days that are equivalent to or exceed plate culture, are robust and reproducible, and can be performed in a variety of laboratory settings. MPN isolates can be obtained for epidemiological investigations. This accessible, non-technical review will be of particular interest to building owners, operators, risk managers, and water safety groups and will enable them to make informed decisions to reduce the risk of L. pneumophila.
Topics: Drinking Water; Humans; Legionella; Legionella pneumophila; Legionnaires' Disease; Water Microbiology
PubMed: 33484265
DOI: 10.1093/jaoacint/qsab003 -
Antimicrobial Agents and Chemotherapy Apr 2020Omadacycline is an aminomethylcycline antibiotic with activity against pathogens causing community-acquired bacterial pneumonia (CABP). This study investigated the...
Omadacycline is an aminomethylcycline antibiotic with activity against pathogens causing community-acquired bacterial pneumonia (CABP). This study investigated the activity of omadacycline against strains isolated between 1995 and 2014 from nosocomial or community-acquired respiratory infections. Omadacycline exhibited extracellular activity similar to comparator antibiotics; intracellular penetrance was found by day 3 of omadacycline exposure. These results support the utility of omadacycline as an effective antibiotic for the treatment of CABP caused by .
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Legionella pneumophila; Legionnaires' Disease; Microbial Sensitivity Tests; Tetracyclines
PubMed: 32094130
DOI: 10.1128/AAC.01972-19 -
European Journal of Immunology Feb 2023Flagellin-induced NAIP/NLRC4 inflammasome activation and pyroptosis are critical events restricting Legionella pneumophila infection. However, the cellular and molecular...
Flagellin-induced NAIP/NLRC4 inflammasome activation and pyroptosis are critical events restricting Legionella pneumophila infection. However, the cellular and molecular dynamics of the in vivo responses against this bacterium are still unclear. We have found temporal coordination of two independent innate immunity pathways in controlling Legionella infection, the inflammasome activation and the CCR2-mediated Mo-DC recruitment. Inflammasome activation was an important player at the early stage of infection by lowering the numbers of bacteria for an efficient bacterial clearance conferred by the Mo-DC at the late stage of the infection. Mo-DC emergence highly depended on CCR2-signaling and dispensed inflammasome activation and pyroptosis. Also, Mo-DC compartment did not rely on the inflammasome machinery to deliver proper immune responses and was the most abundant cytokine-producing among the monocyte-derived cells in the infected lung. Importantly, when the CCR2- and NLRC4-dependent axes of response were simultaneously ablated, we observed an aggravated bacterial burden in the lung of infected mice. Taken together, we showed that inflammasome activation and CCR2-mediated immune response interplay in distinct pathways to restrict pulmonary bacterial infection. These findings extend our understanding of the in vivo integration and cooperation of different innate immunity arms in controlling infectious agents.
Topics: Animals; Mice; Apoptosis Regulatory Proteins; Calcium-Binding Proteins; Chemotaxis, Leukocyte; Dendritic Cells; Inflammasomes; Legionella pneumophila; Legionnaires' Disease; Macrophages; Mice, Knockout; Monocytes; Receptors, CCR2
PubMed: 36427489
DOI: 10.1002/eji.202249985 -
Emerging Infectious Diseases Nov 2017Using the Nationwide Inpatient Sample and US weather data, we estimated the probability of community-acquired pneumonia (CAP) being diagnosed as Legionnaires' disease...
Using the Nationwide Inpatient Sample and US weather data, we estimated the probability of community-acquired pneumonia (CAP) being diagnosed as Legionnaires' disease (LD). LD risk increases when weather is warm and humid. With warm weather, we found a dose-response relationship between relative humidity and the odds for LD. When the mean temperature was 60°-80°F with high humidity (>80.0%), the odds for CAP being diagnosed with LD were 3.1 times higher than with lower levels of humidity (<50.0%). Thus, in some regions (e.g., the Southwest), LD is rarely the cause of hospitalizations. In other regions and seasons (e.g., the mid-Atlantic in summer), LD is much more common. Thus, suspicion for LD should increase when weather is warm and humid. However, when weather is cold, dry, or extremely hot, empirically treating all CAP patients for LD might contribute to excessive antimicrobial drug use at a population level.
Topics: Adolescent; Adult; Aged; Community-Acquired Infections; Female; Hospitalization; Humans; Humidity; Incidence; Legionnaires' Disease; Logistic Models; Male; Middle Aged; Risk; Seasons; Temperature; United States; Weather; Young Adult
PubMed: 29048279
DOI: 10.3201/eid2311.170137 -
International Journal of Environmental... Feb 2022Legionnaires' disease (LD) () is a common cause of community-acquired pneumonia (CAP) in those requiring hospitalization. Geographical variation in the importance of... (Meta-Analysis)
Meta-Analysis Review
Legionnaires' disease (LD) () is a common cause of community-acquired pneumonia (CAP) in those requiring hospitalization. Geographical variation in the importance of species as an aetiologic agent of CAP is poorly understood. We performed a systematic review and meta-analysis of population-based observational studies that reported the proportion of infection in patients with CAP (1 January 1990 to 31 May 2020). Using five electronic databases, articles were identified, appraised and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Univariate and multivariate meta-regression analyses were conducted using study design, WHO region, study quality and healthcare setting as the explanatory variables. We reviewed 2778 studies, of which 219 were included in the meta-analysis. The mean incidence of CAP was 46.7/100,000 population (95% CI: 46.6-46.8). The mean proportion of as the causative agent for CAP was 4.6% (95% CI: 4.4 to 4.7). Consequently, the mean incidence rate was 2.8/100,000 population (95% CI: 2.7-2.9). There was significant heterogeneity across all studies = 99.27% ( < 0.0001). After outliers were removed, there was a decrease in the heterogeneity ( = 43.53%). contribution to CAP has a global distribution. Although the rates appear highest in high income countries in temperate regions, there are insufficient studies from low- and middle-income countries to draw conclusions about the rates in these regions. Nevertheless, this study provides an estimate of the mean incidence of infection in CAP, which could be used to estimate the regional and global burden of LD to support efforts to reduce the impact of this infection as well as to fill important knowledge gaps.
Topics: Community-Acquired Infections; Humans; Legionella; Legionella pneumophila; Legionellosis; Legionnaires' Disease; Pneumonia
PubMed: 35162928
DOI: 10.3390/ijerph19031907 -
Emerging Infectious Diseases Jan 2016During June 2012-September 2014, we tested patients with severe respiratory illness for Legionella spp. infection and conducted a retrospective epidemiologic...
During June 2012-September 2014, we tested patients with severe respiratory illness for Legionella spp. infection and conducted a retrospective epidemiologic investigation. Of 1,805 patients tested, Legionella was detected in samples of 21 (1.2%); most were adults who had HIV or tuberculosis infections and were inappropriately treated for Legionella.
Topics: Child, Preschool; Female; Humans; Legionella; Legionella pneumophila; Legionellosis; Legionnaires' Disease; Male; Respiratory Tract Infections; Retrospective Studies; South Africa
PubMed: 26692504
DOI: 10.3201/eid2201.150972 -
Canadian Journal of Microbiology Dec 2022is a Gram-negative bacterium found in natural and man-made water systems where it replicates within amoebas and ciliates. In humans, once inside the lungs, replicates...
is a Gram-negative bacterium found in natural and man-made water systems where it replicates within amoebas and ciliates. In humans, once inside the lungs, replicates in alveolar macrophages and causes Legionnaires' disease, a severe pneumonia. The Icm/Dot type IVb secretion system is a major virulence factor required for intracellular multiplication. The Icm/Dot system allows the secretion of effectors into the cytoplasm of the host cell. These effectors modify host cell vesicular trafficking and prevent maturation of the phagosome. The innate immune response is crucial in restricting proliferation. TNF-α is one of the major cytokines involved in this process as it renders macrophages more resistant to infection and induces apoptosis of -infected macrophages. Tail-specific proteases (Tsp) are involved in tolerating thermal stress and in virulence. We have previously characterized the Tsp encoded by , showing that it is important for surviving thermal stress and for infection of amoeba when a temperature change occurs during infection. Here, we demonstrated that Tsp is required for intracellular multiplication in macrophages. Absence of is associated with higher production of TNF-α by macrophages in response to infection. This effect is independent of the Icm/Dot secretion system.
Topics: Humans; Legionella pneumophila; Tumor Necrosis Factor-alpha; Legionnaires' Disease; Endopeptidases; Bacterial Proteins
PubMed: 36194898
DOI: 10.1139/cjm-2022-0119