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Frontiers in Microbiology 2023is an opportunistic intracellular pathogen that inhabits artificial water systems and can be transmitted to human hosts by contaminated aerosols. Upon inhalation, it... (Review)
Review
is an opportunistic intracellular pathogen that inhabits artificial water systems and can be transmitted to human hosts by contaminated aerosols. Upon inhalation, it colonizes and grows inside the alveolar macrophages and causes Legionnaires' disease. To effectively control and manage Legionnaires' disease, a deep understanding of the host-pathogen interaction is crucial. Bacterial extracellular vesicles, particularly outer membrane vesicles (OMVs) have emerged as mediators of intercellular communication between bacteria and host cells. These OMVs carry a diverse cargo, including proteins, toxins, virulence factors, and nucleic acids. OMVs play a pivotal role in disease pathogenesis by helping bacteria in colonization, delivering virulence factors into host cells, and modulating host immune responses. This review highlights the role of OMVs in the context of host-pathogen interaction shedding light on the pathogenesis of . Understanding the functions of OMVs and their cargo provides valuable insights into potential therapeutic targets and interventions for combating Legionnaires' disease.
PubMed: 37817751
DOI: 10.3389/fmicb.2023.1270123 -
American Journal of Infection Control Nov 2023Legionella pneumophila is a common cause of community-acquired pneumonia. We aimed to determine the pooled rates of L pneumophila contamination in the water environment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Legionella pneumophila is a common cause of community-acquired pneumonia. We aimed to determine the pooled rates of L pneumophila contamination in the water environment of the hospital.
METHODS
We searched PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, WangFang and Science Direct, The Cochrane Library, and Science Finder, for relevant studies published until December 2022. Stata 16.0 software was used to determine pooled contamination rates, publication bias, and subgroup analysis.
RESULTS
Forty-eight eligible articles with a total of 23,640 samples of water were evaluated, and the prevalence of L pneumophila was 41.6%. The results of the subgroup analysis showed that the pollution rate of L pneumophila in hot water (47.6%) was higher than that in other water bodies. The rates of L pneumophila contamination were higher in developed countries (45.2%), culture methods (42.3%), published between 1985 and 2015 (42.9%), and studies with a sample size of less than 100 (53.0%).
CONCLUSIONS
L pneumophila contamination in medical institutions is still very serious and should be paid attention to, especially in developed countries and hot water tanks.
Topics: Legionella pneumophila; Hospitals; Water Microbiology; Humans; Legionnaires' Disease; Prevalence
PubMed: 37054892
DOI: 10.1016/j.ajic.2023.04.002 -
Cell Reports Aug 2023Xenophagy is an evolutionarily conserved host defensive mechanism to eliminate invading microorganisms through autophagic machinery. The intracellular bacterial pathogen...
Xenophagy is an evolutionarily conserved host defensive mechanism to eliminate invading microorganisms through autophagic machinery. The intracellular bacterial pathogen Legionella pneumophila can avoid clearance by the xenophagy pathway via the actions of multiple Dot/Icm effector proteins. Previous studies have shown that p62, an adaptor protein involved in xenophagy signaling, is excluded from Legionella-containing vacuoles (LCVs). Such defects are attributed to the multifunctional SidE family effectors (SidEs) that exhibit classic deubiquitinase (DUB) and phosphoribosyl ubiquitination (PR-ubiquitination) activities, yet the mechanism remains elusive. In the present study, we demonstrate that the host DUB USP14 is PR-ubiquitinated by SidEs at multiple serine residues, which impairs its DUB activity and its interactions with p62. The exclusion of p62 from the bacterial phagosome requires the ubiquitin ligase but not the DUB activity of SidEs. These results reveal that PR-ubiquitination of USP14 by SidEs contributes to the evasion of xenophagic clearance by L. pneumophila.
Topics: Humans; Legionella; Legionnaires' Disease; Serine; Bacterial Proteins; Ubiquitination; Ubiquitin; Phagosomes; Vacuoles; Ubiquitin Thiolesterase
PubMed: 37471226
DOI: 10.1016/j.celrep.2023.112817 -
Nature Cell Biology Nov 2023A widespread strategy employed by pathogens to establish infection is to inhibit host-cell protein synthesis. Legionella pneumophila, an intracellular bacterial pathogen...
A widespread strategy employed by pathogens to establish infection is to inhibit host-cell protein synthesis. Legionella pneumophila, an intracellular bacterial pathogen and the causative organism of Legionnaires' disease, secretes a subset of protein effectors into host cells that inhibit translation elongation. Mechanistic insights into how the bacterium targets translation elongation remain poorly defined. We report here that the Legionella effector SidI functions in an unprecedented way as a transfer-RNA mimic that directly binds to and glycosylates the ribosome. The 3.1 Å cryo-electron microscopy structure of SidI reveals an N-terminal domain with an 'inverted L' shape and surface-charge distribution characteristic of tRNA mimicry, and a C-terminal domain that adopts a glycosyl transferase fold that licenses SidI to utilize GDP-mannose as a sugar precursor. This coupling of tRNA mimicry and enzymatic action endows SidI with the ability to block protein synthesis with a potency comparable to ricin, one of the most powerful toxins known. In Legionella-infected cells, the translational pausing activated by SidI elicits a stress response signature mimicking the ribotoxic stress response, which is activated by elongation inhibitors that induce ribosome collisions. SidI-mediated effects on the ribosome activate the stress kinases ZAKα and p38, which in turn drive an accumulation of the protein activating transcription factor 3 (ATF3). Intriguingly, ATF3 escapes the translation block imposed by SidI, translocates to the nucleus and orchestrates the transcription of stress-inducible genes that promote cell death, revealing a major role for ATF3 in the response to collided ribosome stress. Together, our findings elucidate a novel mechanism by which a pathogenic bacterium employs tRNA mimicry to hijack a ribosome-to-nuclear signalling pathway that regulates cell fate.
Topics: Humans; Legionella; Cryoelectron Microscopy; Legionella pneumophila; Legionnaires' Disease; Transferases; Bacterial Proteins
PubMed: 37857833
DOI: 10.1038/s41556-023-01248-z -
Acta Bio-medica : Atenei Parmensis Aug 2023Legionnaires' disease is a severe form of pneumonia caused by the inhalation or aspiration of water droplets contaminated with Legionella pneumophila and other...
BACKGROUND AND AIM
Legionnaires' disease is a severe form of pneumonia caused by the inhalation or aspiration of water droplets contaminated with Legionella pneumophila and other Legionella species. These bacteria are commonly found in natural habitats and man-made water systems. Legionnaires' disease is a significant public health problem, especially in healthcare settings where patients may be exposed to contaminated environmental sources. Nosocomial outbreaks have been reported worldwide, leading to high morbidity and mortality rates, and increased healthcare costs. This study aimed to compare, the clonal relationship of clinical L. pneumophila strains from two different hospitals with L. pneumophila strains isolated from the water supply.
METHODS
In the period from 2019 to 2021, clinical and environmental strains involved in three cases of legionellosis were compared by means of pulsed field gel electrophoresis and sequence based typing techniques.
RESULTS
Our findings highlight the persistence of clonally distinct strains within each hospital examined. Furthermore, the L. pneumophila strains detected from hospital environmental sources were related to the clinical strains isolated, demonstrating the nosocomial origin of these cases.
CONCLUSIONS
Therefore, it is important to implement more accurate surveillance systems both for epidemiological studies and to check the effectiveness of remediation procedures. (www.actabiomedica.it).
Topics: Humans; Legionnaires' Disease; Cross Infection; Legionella pneumophila; Water Supply; Water
PubMed: 37773490
DOI: 10.23750/abm.v94iS3.15048 -
Scientific Reports Jul 2023Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a... (Randomized Controlled Trial)
Randomized Controlled Trial
Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a trial of vitamin C supplementation to improve patient outcomes was assessed. Participants with moderate and severe CAP (CURB-65 ≥ 2) on intravenous antimicrobial treatment were randomised to either intravenous vitamin C (2.5 g 8 hourly) or placebo before switching to oral intervention (1 g tds) for 7 days when they were prescribed oral antimicrobial therapy. Of 344 patients screened 75 (22%) were randomised and analysed. The median age was 76 years, and 43 (57%) were male. In each group, one serious adverse event that was potentially intervention related occurred, and one subject discontinued treatment. Vitamin C concentrations were 226 µmol/L in the vitamin C group and 19 µmol/L in the placebo group (p < 0.001) after 3 intravneous doses. There were no signficant differences between the vitamin C and placebo groups for death within 28 days (0 vs. 2; p = 0.49), median length of stay (69 vs. 121 h; p = 0.07), time to clinical stability (22 vs. 49 h; p = 0.08), or readmission within 30 days (1 vs. 4; p = 0.22). The vitamin C doses given were safe, well tolerated and saturating. A randomised controlled trial to assess the efficacy of vitamin C in patients with CAP would require 932 participants (CURB-65 ≥ 2) to observe a difference in mortality and 200 participants to observe a difference with a composite endpoint such as mortality plus discharge after 7 days in hospital. These studies are feasible in a multicentre setting.
Topics: Adult; Humans; Male; Aged; Female; Ascorbic Acid; Feasibility Studies; Pneumonia; Vitamins; Infusions, Intravenous
PubMed: 37482552
DOI: 10.1038/s41598-023-37934-z -
Infection and Drug Resistance 2023We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee...
We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.
PubMed: 37435234
DOI: 10.2147/IDR.S417495 -
The International Journal of... Dec 2023A case admitted with dysarthria and syncope and hyperintense lesion in the splenium of the corpus callosum, diagnosed as Legionnaires' disease by detecting Legionella...
PURPOSE/AIM OF THE STUDY
A case admitted with dysarthria and syncope and hyperintense lesion in the splenium of the corpus callosum, diagnosed as Legionnaires' disease by detecting Legionella antigen in the urine, and recovered only with antibiotic treatment is presented because it is rare in the literature.
MATERIALS AND METHODS
When a 64-year-old female patient was admitted to the emergency department with complaints of sudden loss of consciousness and fainting at home, she had speech impairment, and her pulse oxygen saturation in room air was 88%. In the neurological examination, there was no pathological finding except dysarthria in the patient with no motor deficit. The patient had no respiratory complaints and had a recent travel history. In laboratory examinations, hyponatremia was detected with increased C-reactive protein and liver enzymes. Consolidation was observed in the lower right zone on chest computed tomography. Ampicillin + sulbactam (4x1 gr, intravenous) and clarithromycin (2 × 500 mg orally) were initiated. On cranial magnetic resonance, a hyperintense lesion was observed in the splenium of the corpus callosum in the oval T2 sequence. serogroup 1 antigen in urine was reported as positive. On the fourth day of her hospitalization, the patient, whose CRP and liver enzyme values regressed, her hyponatremia improved, her pulse oxygen saturation increased to 92% in room air, and her speech became comprehensible, was discharged after oral antibiotic treatment was arranged. On the 12 day, the speech ability of the patient completely returned to normal.
CONCLUSION
Legionella infection should be suspected in the presence of pneumonia and corpus callosum splenium lesion.
PubMed: 38060476
DOI: 10.1080/00207454.2023.2292952 -
European Journal of Internal Medicine Feb 2024The optimal antimicrobial regimen for adults with respiratory failure due to Legionella pneumonia remains controversial. A systematic review was performed to assess the...
The optimal antimicrobial regimen for adults with respiratory failure due to Legionella pneumonia remains controversial. A systematic review was performed to assess the impact on outcomes comparing quinolones versus macrolides. A literature search was conducted in PubMed, Cochrane Library and Web of Science between 2012 and 2022. It yielded 124 potentially articles and ten observational studies met the inclusion criteria. A total of 4271 patients were included, 2879 (67 %) were male. A total of 1797 (42 %) subjects required intensive care unit (ICU) admission and 942 (52 %) mechanical ventilation. Fluoroquinolones and macrolides alone were administered in 1397 (33 %) and 1500 (35 %) subjects, respectively; combined therapy in 204 (4.8 %) patients. Overall mortality was 7.4 % (319 patients), with no difference between antibiotics. When data from the three studies with severe pneumonia were pooled together, mortality with fluoroquinolones alone was statistically superior to macrolides alone (72.8 % vs 30.8 %, p value 0.027). Hospital length of stay and complications were comparable. Our findings suggest that macrolides and quinolones were comparable for hospitalized Legionella pneumonia. However, in severe pneumonia, a randomized clinical trial is an unmet clinical need. PROSPERO registration number: CRD42023389308.
Topics: Adult; Humans; Male; Female; Macrolides; Quinolones; Anti-Bacterial Agents; Legionnaires' Disease; Fluoroquinolones; Legionella; Respiratory Insufficiency; Randomized Controlled Trials as Topic
PubMed: 37730517
DOI: 10.1016/j.ejim.2023.09.013 -
The Journal of the Association of... Mar 2024has a higher prevalence in India than in the world. Legionaries' disease most commonly involves the lungs but because of increased awareness, extrapulmonary...
BACKGROUND
has a higher prevalence in India than in the world. Legionaries' disease most commonly involves the lungs but because of increased awareness, extrapulmonary manifestations are also being diagnosed more frequently.
CASE DESCRIPTION
We present a case of a young female with acute onset of fever and chest pain. On initial investigation, an electrocardiogram (ECG) reported widespread pulse rate (PR) depression suggestive of pericarditis which was confirmed by ECG. High-resolution computed tomography (HRCT) thorax suggested mild bilateral pleural effusion with normal lung parenchyma. elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) added to the diagnosis of serositis. Serological study for atypical organisms was remarkable for positive immunoglobulin M (IgM) for . She was treated with a high dose of steroids and azithromycin successfully.
CONCLUSION
Isolated extrapulmonary presentation of legionaries disease is often overlooked and is common. So it should be always included in the diagnostic armamentarium as treatment is highly efficacious if started early.
Topics: Humans; Female; Serositis; Azithromycin; Adult; Anti-Bacterial Agents; Legionellosis; Legionella; Electrocardiography; Tomography, X-Ray Computed; Legionnaires' Disease
PubMed: 38736126
DOI: 10.59556/japi.72.0361