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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 -
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 -
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 -
Travel Medicine and Infectious Disease 2023
Topics: Humans; Legionnaires' Disease; Bacteria; Legionella; Pneumonia; Anti-Bacterial Agents; Community-Acquired Infections
PubMed: 37858711
DOI: 10.1016/j.tmaid.2023.102654 -
Infection and Immunity Nov 2023The host type I interferon (IFN) response protects against infections. Other bacterial pathogens inhibit type I IFN-mediated cell signaling; however, the interaction...
The host type I interferon (IFN) response protects against infections. Other bacterial pathogens inhibit type I IFN-mediated cell signaling; however, the interaction between this signaling pathway and has not been well described. Here, we demonstrate that inhibits the IFN-β signaling pathway but does not inhibit IFN-γ-mediated cell signaling. The addition of IFN-β to -infected macrophages limited bacterial growth independently of NOS2 and reactive nitrogen species. The type IV secretion system of is required to inhibit IFN-β-mediated cell signaling. Finally, we show that the inhibition of the IFN-β signaling pathway occurs downstream of STAT1 and STAT2 phosphorylation. In conclusion, our findings describe a novel host cell signaling pathway inhibited by via its type IV secretion system.
Topics: Humans; Legionella pneumophila; Type IV Secretion Systems; Interferon-gamma; Legionnaires' Disease; Signal Transduction; Interferon Type I
PubMed: 37843413
DOI: 10.1128/iai.00365-23 -
Cureus Sep 2023A lung abscess is characterized as a clinical ailment arising from the localized suppurative necrosis of lung parenchyma. This condition primarily results from the...
A lung abscess is characterized as a clinical ailment arising from the localized suppurative necrosis of lung parenchyma. This condition primarily results from the complications of aspiration pneumonia due to anaerobic microorganisms originating from the oral cavity. Clinically, patients typically manifest symptoms such as fever, malaise, and a productive cough persisting over several weeks. The majority of lung abscess cases acquired within the community stem from anaerobic bacterial infections, often exhibiting a polymicrobial nature. We present a 51-year-old female with intrapulmonary abscess and empyema, with isolation of species. She has a 25-pack-year smoking history. Two weeks prior to arrival at our facility, she experienced intermittent shortness of breath, fever, and subjective fever. Her primary care physician ordered an outpatient computed tomography (CT) which showed evidence of a large right-sided fluid collection. Initial chest X-ray at our facility revealed extensive opacification of the middle and right lower hemithorax, believed to be a large-sized pleural effusion with adjacent pneumonia or atelectasis. She was given a working diagnosis of right-sided empyema. Cardiothoracic surgery was consulted and video-assisted thoracoscopic surgery (VATS) was performed. A very large collection of grossly purulent material was evacuated and revealed a large intrapulmonary abscess. Over 400 cc of frank pus was collected and sent for microbiological analysis. Anaerobic culture demonstrated 3+ species and 3+ species. The genus consists of a small, strictly anaerobic, gram-negative cocci that lacks flagella, spores, and capsules. This genus obtains energy from the utilization of short-chain organic acids that are present in the oral cavity and intestinal tract. Oral is strongly associated with biofilms, causing human oral infectious diseases such as periodontitis and dental caries. Literature states that this organism has been isolated in a limited number of chronic pneumonitis cases. To date, the most common organism isolated from lung abscesses is in adult patients and in pediatric patients. We strive to elucidate the distinctive clinical presentation evident in this case, alongside a comprehensive understanding of the unusual pathogens identified in the disease's pathogenesis.
PubMed: 37842426
DOI: 10.7759/cureus.45210 -
International Journal of Environmental... Oct 2023, the bacterium that causes Legionnaires' disease, can grow and spread in building water systems and devices. The COVID-19 pandemic impacted building water systems...
, the bacterium that causes Legionnaires' disease, can grow and spread in building water systems and devices. The COVID-19 pandemic impacted building water systems through reductions in water usage. growth risk factors can be mitigated through control measures, such as flushing, to address stagnation, as part of a water management program (WMP). A national lodging organization (NLO) provided WMP data, including environmental testing results for periods before and during the pandemic. The statistical analysis revealed an increased risk of water samples testing positive for during the pandemic, with the greatest increase in risk observed at the building's cold-water entry test point. Sample positivity did not vary by season, highlighting the importance of year-round control activities. The NLO's flushing requirements may have prevented an increased risk of growth during the pandemic. However, additional control measures may be needed for some facilities that experience detections. This analysis provides needed evidence for the use of flushing to mitigate the impacts of building water stagnation, as well as the value of routine testing for WMP validation. Furthermore, this report reinforces the idea that WMPs remain the optimal tool to reduce the risk of growth and spread in building water systems.
Topics: United States; Humans; Legionella; Pandemics; COVID-19; Water Microbiology; Legionnaires' Disease; Water Supply; Water; Legionella pneumophila
PubMed: 37835155
DOI: 10.3390/ijerph20196885