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BMC Infectious Diseases May 2022Legionella-related community acquired pneumonia (CAP) is a disease with an increasing incidence and a high mortality rate, especially if empirical antibiotic therapy is...
BACKGROUND
Legionella-related community acquired pneumonia (CAP) is a disease with an increasing incidence and a high mortality rate, especially if empirical antibiotic therapy is inadequate. Antibiotic treatment highly relies on clinical symptoms, although proven non-specific, because currently available diagnostic techniques provide insufficient accuracy for detecting Legionella CAP on admission. This study validates a diagnostic scoring system for detection of Legionella-related CAP, based on six items on admission (Legionella prediction score).
METHODS
We included patients with Legionella-related CAP admitted to five large Dutch hospitals between 2006 and 2016. Controls were non-Legionella-related CAP patients. The following six conditions were rewarded one point if present: fever > 39.4 °C; dry cough; hyponatremia (sodium) < 133 mmol/L; lactate dehydrogenase (LDH) > 225 mmol/L; C-reactive protein (CRP) > 187 mg/L and platelet count < 171 × 10/L. The accuracy of the prediction score was assessed by calculating the area under the curve (AUC) through logistic regression analysis.
RESULTS
We included 131 cases and 160 controls. A score of 0 occurred in non-Legionella-related CAP patients only, a score of 5 and 6 in Legionella-related CAP patients only. A cut-off ≥ 4 resulted in a sensitivity of 58.8% and a specificity of 93.1%. The AUC was 0.89 (95% CI 0.86-0.93). The strongest predictors were elevated LDH, elevated CRP and hyponatremia.
CONCLUSIONS
This multi-centre study validates the Legionella prediction score, an easily applicable diagnostic scoring system, in a large group of patients and finds high diagnostic accuracy. The score shows promise for future prospective validation and could contribute to targeted antibiotic treatment of suspected Legionella CAP.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Humans; Hyponatremia; L-Lactate Dehydrogenase; Legionella; Legionella pneumophila; Legionnaires' Disease; Pneumonia
PubMed: 35534798
DOI: 10.1186/s12879-022-07433-z -
Nature Communications Feb 2022Legionella pneumophila is an intracellular bacterial pathogen that can cause a severe form of pneumonia in humans, a phenotype evolved through interactions with aquatic...
Legionella pneumophila is an intracellular bacterial pathogen that can cause a severe form of pneumonia in humans, a phenotype evolved through interactions with aquatic protozoa in the environment. Here, we show that L. pneumophila uses extracellular vesicles to translocate bacterial small RNAs (sRNAs) into host cells that act on host defence signalling pathways. The bacterial sRNA RsmY binds to the UTR of ddx58 (RIG-I encoding gene) and cRel, while tRNA-Phe binds ddx58 and irak1 collectively reducing expression of RIG-I, IRAK1 and cRel, with subsequent downregulation of IFN-β. Thus, RsmY and tRNA-Phe are bacterial trans-kingdom regulatory RNAs downregulating selected sensor and regulator proteins of the host cell innate immune response. This miRNA-like regulation of the expression of key sensors and regulators of immunity is a feature of L. pneumophila host-pathogen communication and likely represents a general mechanism employed by bacteria that interact with eukaryotic hosts.
Topics: Bacterial Proteins; Cell Line; DEAD Box Protein 58; Eukaryota; Extracellular Vesicles; Host-Pathogen Interactions; Humans; Immunity, Innate; Interleukin-1 Receptor-Associated Kinases; Legionella pneumophila; Legionnaires' Disease; MicroRNAs; Receptors, Immunologic; Signal Transduction
PubMed: 35140216
DOI: 10.1038/s41467-022-28454-x -
Nature Communications Jan 2021Legionella pneumophila infects eukaryotic cells by forming a replicative organelle - the Legionella containing vacuole. During this process, the bacterial protein...
Legionella pneumophila infects eukaryotic cells by forming a replicative organelle - the Legionella containing vacuole. During this process, the bacterial protein DrrA/SidM is secreted and manipulates the activity and post-translational modification (PTM) states of the vesicular trafficking regulator Rab1. As a result, Rab1 is modified with an adenosine monophosphate (AMP), and this process is referred to as AMPylation. Here, we use a chemical approach to stabilise low-affinity Rab:DrrA complexes in a site-specific manner to gain insight into the molecular basis of the interaction between the Rab protein and the AMPylation domain of DrrA. The crystal structure of the Rab:DrrA complex reveals a previously unknown non-conventional Rab-binding site (NC-RBS). Biochemical characterisation demonstrates allosteric stimulation of the AMPylation activity of DrrA via Rab binding to the NC-RBS. We speculate that allosteric control of DrrA could in principle prevent random and potentially cytotoxic AMPylation in the host, thereby perhaps ensuring efficient infection by Legionella.
Topics: Adenosine Monophosphate; Allosteric Regulation; Bacterial Proteins; Binding Sites; Crystallography, X-Ray; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate; Humans; Legionella pneumophila; Legionnaires' Disease; Macrophages, Alveolar; Phagocytosis; Protein Binding; Protein Processing, Post-Translational; Recombinant Proteins; rab1 GTP-Binding Proteins
PubMed: 33469029
DOI: 10.1038/s41467-020-20702-2 -
Emerging Infectious Diseases Jun 2023Legionellosis, notably Legionnaires' disease, is recognized globally and in New Zealand (Aotearoa) as a major cause of community-acquired pneumonia. We analyzed the...
Legionellosis, notably Legionnaires' disease, is recognized globally and in New Zealand (Aotearoa) as a major cause of community-acquired pneumonia. We analyzed the temporal, geographic, and demographic epidemiology and microbiology of Legionnaires' disease in New Zealand by using notification and laboratory-based surveillance data for 2000‒2020. We used Poisson regression models to estimate incidence rate ratios and 95% CIs to compare demographic and organism trends over 2 time periods (2000-2009 and 2010-2020). The mean annual incidence rate increased from 1.6 cases/100,000 population for 2000-2009 to 3.9 cases/100,000 population for 2010-2020. This increase corresponded with a change in diagnostic testing from predominantly serology with some culture to almost entirely molecular methods using PCR. There was also a marked shift in the identified dominant causative organism, from Legionella pneumophila to L. longbeachae. Surveillance for legionellosis could be further enhanced by greater use of molecular typing of isolates.
Topics: Humans; Legionnaires' Disease; New Zealand; Incidence; Legionellosis; Legionella pneumophila
PubMed: 37209673
DOI: 10.3201/eid2906.221598 -
International Journal of Environmental... Jun 2021Legionnaires' disease (LD) is a severe pneumonia caused by bacteria belonging to the genus . This is a major public health concern and infections are steadily increasing...
Legionnaires' disease (LD) is a severe pneumonia caused by bacteria belonging to the genus . This is a major public health concern and infections are steadily increasing worldwide. Several sources of infection have been identified, but they have not always been linked to human isolates by molecular match. The well-known contamination of private homes has rarely been associated with the acquisition of the disease, although some patients never left their homes during the incubation period. This study demonstrated by genomic matching between clinical and environmental isolates that the source of an LD cluster was a private building. Monoclonal antibodies and sequence-based typing were used to type the isolates, and the results clearly demonstrated the molecular relationship between the strains highlighting the risk of contracting LD at home. To contain this risk, the new European directive on the quality of water intended for human consumption has introduced for the first time as a microbiological parameter to be investigated in domestic water systems. This should lead to a greater attention to prevention and control measures for domestic contamination and, consequently, to a possible reduction in community acquired LD cases.
Topics: Disease Hotspot; Genomics; Humans; Italy; Legionella pneumophila; Legionnaires' Disease; Water Microbiology
PubMed: 34203343
DOI: 10.3390/ijerph18136922 -
Environmental Health Perspectives Dec 2019A community-wide outbreak of Legionnaires' disease (LD) occurred in Genesee County, Michigan, in 2014 and 2015. Previous reports about the outbreak are conflicting and...
BACKGROUND
A community-wide outbreak of Legionnaires' disease (LD) occurred in Genesee County, Michigan, in 2014 and 2015. Previous reports about the outbreak are conflicting and have associated the outbreak with a change of water source in the city of Flint and, alternatively, to a Flint hospital.
OBJECTIVE
The objective of this investigation was to independently identify relevant sources of that likely resulted in the outbreak.
METHODS
An independent, retrospective investigation of the outbreak was conducted, making use of public health, health care, and environmental data and whole-genome multilocus sequence typing (wgMLST) of clinical and environmental isolates.
RESULTS
Strong evidence was found for a hospital-associated outbreak in both 2014 and 2015: ) 49% of cases had prior exposure to Flint hospital A, significantly higher than expected from Medicare admissions; ) hospital plumbing contained high levels of ; ) control measures in hospital plumbing aligned with subsidence of hospital A-associated cases; and ) wgMLST showed isolates from cases exposed to hospital A and from hospital plumbing to be highly similar. Multivariate analysis showed an increased risk of LD in 2014 for people residing in a home that received Flint water or was located in proximity to several Flint cooling towers.
DISCUSSION
This is the first LD outbreak in the United States with evidence for three sources (in 2014): ) exposure to hospital A, ) receiving Flint water at home, and ) residential proximity to cooling towers; however, for 2015, evidence points to hospital A only. Each source could be associated with only a proportion of cases. A focus on a single source may have delayed recognition and remediation of other significant sources of . https://doi.org/10.1289/EHP5663.
Topics: Disease Outbreaks; Humans; Legionella pneumophila; Legionnaires' Disease; Medicare; Michigan; Retrospective Studies; United States
PubMed: 31799878
DOI: 10.1289/EHP5663 -
The American Journal of Case Reports Sep 2023BACKGROUND Legionnaires' disease is one of the most common types of community-acquired pneumonia. It can cause acute kidney injury and also occasionally become severe...
BACKGROUND Legionnaires' disease is one of the most common types of community-acquired pneumonia. It can cause acute kidney injury and also occasionally become severe enough to require continuous renal replacement therapy (CRRT). Non-occlusive mesenteric ischemia (NOMI) is a condition characterized by ischemia and necrosis of the intestinal tract without organic obstruction of the mesenteric vessels and is known to have a high mortality rate. CASE REPORT A 72-year-old man with fatigue and dyspnea was diagnosed with Legionnaires' disease after a positive result in the Legionella urinary antigen test pneumonia confirmed by chest radiography and computed tomography. He developed acute kidney injury, with anuria, rhabdomyolysis, septic shock, respiratory failure, and metabolic acidosis. We initiated treatment with antibiotics, catecholamines, mechanical ventilation, CRRT, steroid therapy, and endotoxin absorption therapy in the Intensive Care Unit. Despite ongoing CRRT, metabolic acidosis did not improve. The patient was unresponsive to treatment and died 5 days after admission. The autopsy revealed myoglobin nephropathy, multiple organ failure, and NOMI. CONCLUSIONS We report a fatal case of Legionnaires' disease complicated by rhabdomyolysis, acute kidney injury, myoglobin cast nephropathy, and NOMI. Legionella pneumonia complicated by acute kidney injury is associated with a high mortality rate. In the present case, this may have been further exacerbated by the complication of NOMI. In our clinical practice, CRRT is a treatment option for septic shock complicated by acute kidney injury. Thus, it is crucial to suspect the presence of NOMI when persistent metabolic acidosis is observed, despite continuous CRRT treatment.
Topics: Male; Humans; Aged; Legionnaires' Disease; Mesenteric Ischemia; Myoglobin; Shock, Septic; Rhabdomyolysis; Acute Kidney Injury
PubMed: 37742066
DOI: 10.12659/AJCR.940792 -
Proteins Feb 2018Legionella pneumophila is a pathogen causing severe pneumonia in humans called Legionnaires' disease. Lem22 is a previously uncharacterized effector protein conserved in...
Legionella pneumophila is a pathogen causing severe pneumonia in humans called Legionnaires' disease. Lem22 is a previously uncharacterized effector protein conserved in multiple Legionella strains. Here, we report the crystal structure of Lem22 from the Philadelphia strain, also known as lpg2328, at 1.40 Å resolution. The structure shows an up-and-down three-helical bundle with a significant structural similarity to a number of protein-binding domains involved in apoptosis and membrane trafficking. Sequence conservation identifies a putative functional site on the interface of helices 2 and 3. The structure is an important step toward a functional characterization of Lem22.
Topics: Amino Acid Sequence; Bacterial Proteins; Crystallization; Crystallography, X-Ray; Humans; Legionella pneumophila; Legionnaires' Disease; Models, Molecular; Protein Conformation
PubMed: 29159828
DOI: 10.1002/prot.25427 -
Nature Communications Dec 2021Legionella pneumophila is the most common cause of the severe respiratory infection known as Legionnaires' disease. However, the microorganism is typically a symbiont of...
Legionella pneumophila is the most common cause of the severe respiratory infection known as Legionnaires' disease. However, the microorganism is typically a symbiont of free-living amoeba, and our understanding of the bacterial factors that determine human pathogenicity is limited. Here we carried out a population genomic study of 902 L. pneumophila isolates from human clinical and environmental samples to examine their genetic diversity, global distribution and the basis for human pathogenicity. We find that the capacity for human disease is representative of the breadth of species diversity although some clones are more commonly associated with clinical infections. We identified a single gene (lag-1) to be most strongly associated with clinical isolates. lag-1, which encodes an O-acetyltransferase for lipopolysaccharide modification, has been distributed horizontally across all major phylogenetic clades of L. pneumophila by frequent recent recombination events. The gene confers resistance to complement-mediated killing in human serum by inhibiting deposition of classical pathway molecules on the bacterial surface. Furthermore, acquisition of lag-1 inhibits complement-dependent phagocytosis by human neutrophils, and promoted survival in a mouse model of pulmonary legionellosis. Thus, our results reveal L. pneumophila genetic traits linked to disease and provide a molecular basis for resistance to complement-mediated killing.
Topics: Acetyltransferases; Animals; Bacterial Proteins; Complement System Proteins; Female; Genome, Bacterial; Humans; Legionella pneumophila; Legionnaires' Disease; Mice; Mice, Inbred C57BL; Neutrophils; Phylogeny
PubMed: 34887398
DOI: 10.1038/s41467-021-27478-z -
Environmental Research Nov 2021Legionellosis is a severe pneumonia caused by the inhalation of aerosols containing Legionella, Gram-negative bacteria present in the water systems of...
Legionellosis is a severe pneumonia caused by the inhalation of aerosols containing Legionella, Gram-negative bacteria present in the water systems of touristic-recreational facilities. The purpose of this study was to develop a scoring tool to predict the risk of both environmental contamination and Legionnaires' disease cases in such facilities in the Apulia region of southern Italy. We analyzed 47 structural and management parameters/risk factors related to the buildings, water systems, and air conditioning at the facilities. A Poisson regression model was used to compute an overall risk score for each facility with respect to three outcomes: water samples positive for Legionella (risk score range: 7-54), water samples positive for Legionella with an average load exceeding 1000 colony-forming units per liter (CFU/L) (risk score range: 22-179,871), and clinical cases of Legionnaire's disease (risk score range: 6-31). The cut-off values for three outcomes were determined by receiver operating characteristic curves (first outcome, samples positive for Legionella in a touristic-recreational facility: 19; second outcome, samples positive for Legionella in a touristic-recreational facility with an average load exceeding 1000 CFU/L: 2062; third outcome, clinical cases of Legionnaire's disease in a touristic-recreational facility: 22). Above these values, there was a significant probability of observing the outcome. We constructed this predictive model using 70% of a large dataset (18 years of clinical and environmental surveillance) and tested the model on the remaining 30% of the dataset to demonstrate its reliability. Our model enables the assessment of risk for a touristic facility and the creation of a conceptual framework to link the risk analysis with prevention measures.
Topics: Humans; Legionella; Legionella pneumophila; Legionellosis; Legionnaires' Disease; Reproducibility of Results; Risk Assessment; Water Microbiology
PubMed: 34252427
DOI: 10.1016/j.envres.2021.111649