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MMWR. Morbidity and Mortality Weekly... Dec 2023Legionnaires disease is a serious infection acquired by inhalation of water droplets from human-made building water systems that contain Legionella bacteria. On July 11...
Legionnaires disease is a serious infection acquired by inhalation of water droplets from human-made building water systems that contain Legionella bacteria. On July 11 and 12, 2022, Napa County Public Health (NCPH) in California received reports of three positive urinary antigen tests for Legionella pneumophila serogroup 1 in the town of Napa. By July 21, six Legionnaires disease cases had been confirmed among Napa County residents, compared with a baseline of one or two cases per year. NCPH requested assistance from the California Department of Public Health (CDPH) and CDC to aid in the investigations. Close temporal and geospatial clustering permitted a focused environmental sampling strategy of high-risk facilities which, coupled with whole genome sequencing results from samples and investigation of water system maintenance, facilitated potential linking of the outbreak with an environmental source. NCPH, with technical support from CDC and CDPH, instructed and monitored remediation practices for all environmental locations that tested positive for Legionella. The investigation response to this community outbreak illustrates the importance of interdisciplinary collaboration by public health agencies, laboratory support, timely communication with the public, and cooperation of managers of potentially implicated water systems. Timely identification of possible sources, sampling, and remediation of any facility testing positive for Legionella is crucial to interrupting further transmission.
Topics: Humans; Legionnaires' Disease; Legionella pneumophila; Legionella; Disease Outbreaks; Water Microbiology; California; Water
PubMed: 38060434
DOI: 10.15585/mmwr.mm7249a1 -
BioRxiv : the Preprint Server For... Nov 2023is an accidental human bacterial pathogen that infects and replicates within alveolar macrophages causing a severe atypical pneumonia known as Legionnaires' disease. As...
is an accidental human bacterial pathogen that infects and replicates within alveolar macrophages causing a severe atypical pneumonia known as Legionnaires' disease. As a prototypical vacuolar pathogen establishes a unique endoplasmic reticulum (ER)-derived organelle within which bacterial replication takes place. Bacteria-derived proteins are deposited in the host cytosol and in the lumen of the pathogen-occupied vacuole via a type IVb (T4bSS) and a type II (T2SS) secretion system respectively. These secretion system effector proteins manipulate multiple host functions to facilitate intracellular survival of the bacteria. Subversion of host membrane glycerophospholipids (GPLs) by the internalized bacteria via distinct mechanisms feature prominently in trafficking and biogenesis of the -containing vacuole (LCV). Conventional GPLs composed of a glycerol backbone linked to a polar headgroup and esterified with two fatty acids constitute the bulk of membrane lipids in eukaryotic cells. The acyl chain composition of GPLs dictates phase separation of the lipid bilayer and therefore determines the physiochemical properties of biological membranes - such as membrane disorder, fluidity and permeability. In mammalian cells, fatty acids esterified in membrane GPLs are sourced endogenously from synthesis or via internalization from the exogenous pool of lipids present in serum and other interstitial fluids. Here, we exploited the preferential utilization of exogenous fatty acids for GPL synthesis by macrophages to reprogram the acyl chain composition of host membranes and investigated its impact on LCV homeostasis and intracellular replication. Using saturated fatty acids as well as - and - isomers of monounsaturated fatty acids we discovered that under conditions promoting lipid packing and membrane rigidification intracellular replication was significantly reduced. Palmitoleic acid - a C16:1 monounsaturated fatty acid - that promotes membrane disorder when enriched in GPLs significantly increased bacterial replication within human and murine macrophages but not in axenic growth assays. Lipidome analysis of infected macrophages showed that treatment with exogenous palmitoleic acid resulted in membrane acyl chain reprogramming in a manner that promotes membrane disorder and live-cell imaging revealed that the consequences of increasing membrane disorder impinge on several LCV homeostasis parameters. Collectively, we provide experimental evidence that replication within its intracellular niche is a function of the lipid bilayer disorder and hydrophobic thickness.
PubMed: 38045297
DOI: 10.1101/2023.11.19.567753 -
Annals of Clinical Microbiology and... Nov 2023Legionnaires' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary... (Review)
Review
BACKGROUND
Legionnaires' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary cavitary LD.
METHODS
A research strategy was developed and applied to the databases Embase, Pubmed, and Web of Science from the 1st of January 2000 to the 1st of November 2022. Original articles, case series, case reports, and guidelines written in English, French, German, Italian, and Dutch were considered. Furthermore, medical records of patients treated at the University Hospital UZ Brussel for LD cavitary pneumonia, between the 1st of January 2016 to the 1st of January 2022, were reviewed.
RESULTS
Two patients were found by the UZ Brussel's medical records investigation. Through the literature review, 23 reports describing 29 patients, and seven guidelines were identified. The overall evidence level was low.
RESULT OF SYNTHESIS (CASE REPORTS)
The median age was 48 years and 65% were male. A polymicrobial infection was detected in 11 patients (44%) with other aerobic bacteria being the most commonly found. At diagnosis, 52% of patients received combination therapy, and fluoroquinolones were the preferred antimicrobial class. Anaerobic coverage was neglected in 33% of patients.
RESULT OF SYNTHESIS (GUIDELINES)
Three guidelines favor monotherapy with fluoroquinolones or macrolides, while one suggested an antimicrobial combination in case of severe LD. Four guidelines recommended anaerobic coverage in case of lung abscesses.
CONCLUSION
To date, the evidence supporting cavitary LD treatment is low. Monotherapy lowers toxicity and might be as effective as combination therapy. Finally, anaerobes should not be neglected.
Topics: Humans; Male; Middle Aged; Female; Legionnaires' Disease; Pneumonia; Anti-Bacterial Agents; Fluoroquinolones; Macrolides
PubMed: 38031167
DOI: 10.1186/s12941-023-00652-5 -
Japanese Journal of Infectious Diseases Mar 2024Legionella pneumophila serogroup (SG) 1, the main cause of Legionnaires' disease, can be diagnosed using urinary antigen testing kits. However, lower respiratory tract...
Legionella pneumophila serogroup (SG) 1, the main cause of Legionnaires' disease, can be diagnosed using urinary antigen testing kits. However, lower respiratory tract specimen cultures are required to identify L. pneumophila SG 2-15. We attempted to detect L. pneumophila SG-specific genes in a culture-negative sputum specimen from a patient with pneumonia who was suspected to have Legionnaires' disease. Two multiplex PCR methods targeting L. pneumophila were modified and amplicons considered to be SG13 specific were detected. Direct sequencing revealed that the amplicons were identical to the nucleotide sequence of L. pneumophila SG13. Based on the presentation and clinical course (fever, muscle pain, disturbance of consciousness, high C-reactive protein titer, rhabdomyolysis, hypophosphatemia, and symptomatic improvement with levofloxacin treatment), in combination with the detection of L. pneumophila SG-specific genes, we suspected L. pneumophila SG13 pneumonia. L. pneumophila non-SG1 pneumonia is thought to be underestimated because of its difficult laboratory diagnosis. The modified multiplex PCR system for lower respiratory tract specimens revealed in this study is likely to improve the diagnosis of Legionnaires' disease caused by L. pneumophila SG13 and other SGs.
Topics: Humans; Legionella pneumophila; Legionnaires' Disease; Serogroup; Sputum; Pneumonia
PubMed: 38030269
DOI: 10.7883/yoken.JJID.2023.302 -
New Microbes and New Infections Oct 2023
PubMed: 38024335
DOI: 10.1016/j.nmni.2023.101194 -
Tropical Medicine and Infectious Disease Oct 2023A bacterium is ubiquitous in water distribution systems, including dental unit waterlines (DUWLs). Legionellosis is atypical pneumonia, including Legionnaires' disease...
A bacterium is ubiquitous in water distribution systems, including dental unit waterlines (DUWLs). Legionellosis is atypical pneumonia, including Legionnaires' disease (LD) and the less acute form of Pontiac fever. Legionellosis occurs as a result of inhalation/aspiration of aerosolized -contaminated water by susceptible patients, health workers, and dentists. In this study, we undertook to determine the prevalence of in water and biofilm samples from Tap and DUWLs collected from five sites of dental clinics and faculties across the West Bank. Water samples were tested for physical and chemical parameters. The study samples included 185 samples, 89 (48%) water samples, and 96 (52%) biofilm swabs, which were analyzed by cultivation-dependent analysis (CDA) and by the cultivation-independent technique (CIA). Also, partial sequencing of the 16S rRNA gene for fifteen isolates was performed for quality assurance and identification. was isolated from 28 (15%) of 185 samples using CDA and was detected in 142 (77%) of 185 samples using CIA. The abundance of culturable was low in DUWL of the sampling sites (range: 27-115 CFU/Liter). PCR was 5× more sensitive than the culture technique. Sg 1 was detected in (75%) of the isolates, while (25%) isolates were Sg 2-14. All fifteen sequenced isolates were identified as ≥ 94.5%. The analysis of phylogenetic tree showed that branch clearly identified and distinguished from other branches. These results show that DUWLs of the examined dental clinics and faculties are contaminated with . This finding reveals a serious potential health risk for infection of immunocompromised patients and dentists' post-exposure.
PubMed: 37999609
DOI: 10.3390/tropicalmed8110490 -
Frontiers in Cellular and Infection... 2023Severe Legionnaires' disease (LD) can lead to multi-organ failure or death in 10%-30% of patients. Although hyper-inflammation and immunoparalysis are well described in...
INTRODUCTION
Severe Legionnaires' disease (LD) can lead to multi-organ failure or death in 10%-30% of patients. Although hyper-inflammation and immunoparalysis are well described in sepsis and are associated with high disease severity, little is known about the immune response in LD. This study aimed to evaluate the immune status of patients with LD and its association with disease severity.
METHODS
A total of 92 hospitalized LD patients were included; 19 plasmatic cytokines and pulmonary DNA load were measured in 84 patients on the day of inclusion (day 0, D0). Immune functional assays (IFAs) were performed from whole blood samples collected at D2 and stimulated with concanavalin A [conA, = 19 patients and = 21 healthy volunteers (HV)] or lipopolysaccharide (LPS, = 14 patients and = 9 HV). A total of 19 cytokines (conA stimulation) and TNF-α (LPS stimulation) were quantified from the supernatants. The Sequential Organ Failure Assessment (SOFA) severity score was recorded at D0 and the mechanical ventilation (MV) status was recorded at D0 and D8.
RESULTS
Among the 84 patients, a higher secretion of plasmatic MCP-1, MIP1-β, IL-6, IL-8, IFN-γ, TNF-α, and IL-17 was observed in the patients with D0 and D8 MV. Multiparametric analysis showed that these seven cytokines were positively associated with the SOFA score. Upon conA stimulation, LD patients had a lower secretion capacity for 16 of the 19 quantified cytokines and a higher release of IL-18 and MCP-1 compared to HV. IL-18 secretion was higher in D0 and D8 MV patients. TNF-α secretion, measured after LPS stimulation, was significantly reduced in LD patients and was associated with D8 MV status.
DISCUSSION
The present findings describe a hyper-inflammatory phase at the initial phase of pneumonia that is more pronounced in patients with severe LD. These patients also present an immunoparalysis for a large number of cytokines, except IL-18 whose secretion is increased. An assessment of the immune response may be relevant to identify patients eligible for future innovative host-directed therapies.
Topics: Humans; Interleukin-18; Tumor Necrosis Factor-alpha; Lipopolysaccharides; Legionnaires' Disease; Cytokines
PubMed: 37965258
DOI: 10.3389/fcimb.2023.1252515 -
The Journal of Hospital Infection Nov 2023Legionella pneumophila is a water-borne bacterium that can cause Legionnaires' disease. Legiolert® (IDEXX, USA) is a low-labour liquid culture assay for the detection...
Concordance between IDEXX Legiolert® (liquid culture assay) and plate culture (ISO 11731:2017) for the detection and quantification of Legionella pneumophila in water samples.
BACKGROUND
Legionella pneumophila is a water-borne bacterium that can cause Legionnaires' disease. Legiolert® (IDEXX, USA) is a low-labour liquid culture assay for the detection and enumeration of L. pneumophila (SG1-15) from water.
AIM
To analyse concordance between Legiolert and ISO 11731:2017 plate culture method (membrane filtration and culture on selective agars) using hospital water samples (N = 100).
METHODS
Incubation was at 39 °C and 36 °C, respectively, for seven days, followed by most-probable enumeration for Legiolert and subculturing and serogrouping of suspected Legionella colonies, with plate culture.
FINDINGS
L. pneumophila (SG1-15) was isolated from 25 out of 100 samples when using Legiolert or plate culture. Fourteen additional Legiolert samples tested positive for L. pneumophila; analysis of the same samples by plate culture was negative (12 out of 14) or yielded only Legionella rubrilucens (two out of 14; confirmed via matrix-assisted ionization/desorption time-of-flight mass spectrometry). L. pneumophila was not captured from Quanti-Tray/Legiolert pouch wells of these positive samples after subculture of puncture aliquots on buffered charcoal yeast-extract agar. Both methods in concordance did not detect L. pneumophila in 61 out of 100 samples.
CONCLUSION
Legiolert and plate culture are both satisfactory methods to detect L. pneumophila from water samples, and both to detect isolated L. pneumophila in 25% of the sample population. Legiolert provides a faster time to result, and is less resource-demanding and labour-intensive; however, there may be a low risk of cross-reactivity with other organisms. Both methods are suitable for the analysis of water in healthcare settings, where the monitoring of L. pneumophila is imperative in preventing cases of Legionnaires' disease.
PubMed: 37949373
DOI: 10.1016/j.jhin.2023.10.019 -
European Journal of Cell Biology Dec 2023The study of virulence of Legionella pneumophila and its interactions with its hosts has been predominantly conducted in cellulo in the past decades. Although easy to... (Review)
Review
The study of virulence of Legionella pneumophila and its interactions with its hosts has been predominantly conducted in cellulo in the past decades. Although easy to implement and allowing the dissection of molecular pathways underlying host-pathogen interactions, these cellular models fail to provide conditions of the complex environments encountered by the bacteria during the infection of multicellular organisms. To improve our understanding of human infection, several animal models have been developed. This review provides an overview of the invertebrate and vertebrate models that have been established to study L. pneumophila infection and that are alternatives to the classical mouse model, which does not recall human infection with L. pneumophila well. Finally we provide insight in the main contributions made by these models along with their pros and cons.
Topics: Animals; Mice; Humans; Legionnaires' Disease; Legionella pneumophila; Invertebrates; Vertebrates; Disease Models, Animal
PubMed: 37926040
DOI: 10.1016/j.ejcb.2023.151369 -
Nature Communications Nov 2023Legionella pneumophila (LP) secretes more than 300 effectors into the host cytosol to facilitate intracellular replication. One of these effectors, SidH, 253 kDa in...
Legionella pneumophila (LP) secretes more than 300 effectors into the host cytosol to facilitate intracellular replication. One of these effectors, SidH, 253 kDa in size with no sequence similarity to proteins of known function is toxic when overexpressed in host cells. SidH is regulated by the LP metaeffector LubX which targets SidH for degradation in a temporal manner during LP infection. The mechanism underlying the toxicity of SidH and its role in LP infection are unknown. Here, we determined the cryo-EM structure of SidH at 2.7 Å revealing a unique alpha helical arrangement with no overall similarity to known protein structures. Surprisingly, purified SidH came bound to a E. coli EF-Tu/t-RNA/GTP ternary complex which could be modeled into the cryo-EM density. Mutation of residues disrupting the SidH-tRNA interface and SidH-EF-Tu interface abolish the toxicity of overexpressed SidH in human cells, a phenotype confirmed in infection of Acanthamoeba castellani. We also present the cryo-EM structure of SidH in complex with a U-box domain containing ubiquitin ligase LubX delineating the mechanism of regulation of SidH. Our data provide the basis for the toxicity of SidH and into its regulation by the metaeffector LubX.
Topics: Humans; Legionella pneumophila; Escherichia coli; Peptide Elongation Factor Tu; Legionnaires' Disease; Ubiquitin-Protein Ligases; Bacterial Proteins
PubMed: 37923743
DOI: 10.1038/s41467-023-42683-8