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Current Opinion in Environmental... Apr 2022Due to the SARS-CoV-2 pandemic and restricted occupancy in work and school settings, there is a heightened risk for infection. An increase of stagnation in water pipe... (Review)
Review
Due to the SARS-CoV-2 pandemic and restricted occupancy in work and school settings, there is a heightened risk for infection. An increase of stagnation in water pipe systems with limited water usage stimulates biofilm build-up, further facilitating proliferation. Individuals can inhale infected water aerosols and develop Legionellosis that can progress into mild flu-like symptoms or severe pneumonia. While SARS-CoV-2 vaccinations have been introduced globally, there is a concern for bacterial coinfections as individuals resume normal activities. Even with new SARS-CoV-2 variants circulating, persists as a public health threat as vulnerable communities' restrictions fluctuate. Proper water monitoring and management are critical while reopening communities. This article features characteristics and novel case reports amidst the pandemic. This article encourages greater awareness for building managers to minimize water stagnancy by disinfecting water distribution systems and promotes healthcare professionals to properly diagnose other illnesses during the ongoing pandemic to reduce morbidity and mortality.
PubMed: 35155880
DOI: 10.1016/j.coesh.2022.100328 -
MicroLife 2023Vesicular trafficking and membrane fusion are well-characterized, versatile, and sophisticated means of 'long range' intracellular protein and lipid delivery. Membrane... (Review)
Review
Vesicular trafficking and membrane fusion are well-characterized, versatile, and sophisticated means of 'long range' intracellular protein and lipid delivery. Membrane contact sites (MCS) have been studied in far less detail, but are crucial for 'short range' (10-30 nm) communication between organelles, as well as between pathogen vacuoles and organelles. MCS are specialized in the non-vesicular trafficking of small molecules such as calcium and lipids. Pivotal MCS components important for lipid transfer are the VAP receptor/tether protein, oxysterol binding proteins (OSBPs), the ceramide transport protein CERT, the phosphoinositide phosphatase Sac1, and the lipid phosphatidylinositol 4-phosphate (PtdIns(4)). In this review, we discuss how these MCS components are subverted by bacterial pathogens and their secreted effector proteins to promote intracellular survival and replication.
PubMed: 37223745
DOI: 10.1093/femsml/uqad018 -
Nature Communications Apr 2023Legionella pneumophila replicates intracellularly by secreting effectors via a type IV secretion system. One of these effectors is a eukaryotic methyltransferase (RomA)...
Legionella pneumophila replicates intracellularly by secreting effectors via a type IV secretion system. One of these effectors is a eukaryotic methyltransferase (RomA) that methylates K14 of histone H3 (H3K14me3) to counteract host immune responses. However, it is not known how L. pneumophila infection catalyses H3K14 methylation as this residue is usually acetylated. Here we show that L. pneumophila secretes a eukaryotic-like histone deacetylase (LphD) that specifically targets H3K14ac and works in synergy with RomA. Both effectors target host chromatin and bind the HBO1 histone acetyltransferase complex that acetylates H3K14. Full activity of RomA is dependent on the presence of LphD as H3K14 methylation levels are significantly decreased in a ∆lphD mutant. The dependency of these two chromatin-modifying effectors on each other is further substantiated by mutational and virulence assays revealing that the presence of only one of these two effectors impairs intracellular replication, while a double knockout (∆lphD∆romA) can restore intracellular replication. Uniquely, we present evidence for "para-effectors", an effector pair, that actively and coordinately modify host histones to hijack the host response. The identification of epigenetic marks modulated by pathogens has the potential to lead to the development of innovative therapeutic strategies to counteract bacterial infection and strengthening host defences.
Topics: Humans; Legionella; Chromatin; Bacterial Proteins; Legionella pneumophila; Legionnaires' Disease; Histones
PubMed: 37059817
DOI: 10.1038/s41467-023-37885-z -
Emerging Infectious Diseases Oct 2020Healthcare-associated Legionnaires' disease (HCA LD) can cause nosocomial outbreaks with high death rates. We compared community-acquired LD cases with HCA LD cases in...
Healthcare-associated Legionnaires' disease (HCA LD) can cause nosocomial outbreaks with high death rates. We compared community-acquired LD cases with HCA LD cases in Europe during 2008-2017 using data from The European Surveillance System. A total of 29 countries reported 40,411 community-acquired and 4,315 HCA LD cases. Of the HCA LD cases, 2,937 (68.1%) were hospital-acquired and 1,378 (31.9%) were linked to other healthcare facilities. The odds of having HCA LD were higher for women, children and persons <20 years of age, and persons >60 years of age. Out of the cases caused by Legionella pneumophila with a known serotype, community-acquired LD was more likely to be caused by L. pneumophila serogroup 1 (92.3%) than was HCA LD (85.1%). HCA LD patients were more likely to die. HCA LD is associated with specific patient demographics, causative strains, and outcomes. Healthcare facilities should consider these characteristics when designing HCA LD prevention strategies.
Topics: Child; Delivery of Health Care; Disease Outbreaks; Europe; Female; Humans; Legionella pneumophila; Legionnaires' Disease
PubMed: 32946366
DOI: 10.3201/eid2610.181889 -
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 -
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 -
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 -
Virulence Dec 2021Bacteria of the genus are natural pathogens of amoebae that can cause a severe pneumonia in humans called Legionnaires' Disease. Human disease results from inhalation... (Review)
Review
Bacteria of the genus are natural pathogens of amoebae that can cause a severe pneumonia in humans called Legionnaires' Disease. Human disease results from inhalation of -contaminated aerosols and subsequent bacterial replication within alveolar macrophages. pathogenicity in humans has resulted from extensive co-evolution with diverse genera of amoebae. To replicate intracellularly, generates a replication-permissive compartment called the -containing vacuole (LCV) through the concerted action of hundreds of Dot/Icm-translocated effector proteins. In this review, we present a collective overview of pathogenicity including infection mechanisms, secretion systems, and translocated effector function. We also discuss innate and adaptive immune responses to , the implications of genome diversity and future avenues for the field.
Topics: Humans; Immunity; Legionella; Legionnaires' Disease; Vacuoles; Virulence
PubMed: 33843434
DOI: 10.1080/21505594.2021.1903199 -
Microorganisms Jun 2023Legionellosis is a respiratory disease of bacterial and environmental origin that usually presents two distinct clinical entities, "Legionnaires' disease" (LD) and...
Legionellosis is a respiratory disease of bacterial and environmental origin that usually presents two distinct clinical entities, "Legionnaires' disease" (LD) and "Pontiac fever". LD is an important cause of hospital-acquired pneumonia (HAP). The objective of this study is to describe the epidemiology of legionellosis-associated hospitalization (L-AH) in Spain from 2002 to 2021 and the burden of hospitalization due to legionellosis. Discharge reports from the Minimum Basic Data Set (MBDS) were used to retrospectively analyze hospital discharge data with a diagnosis of legionellosis, based on the ICD-9-CM and ICD-10-CM diagnosis codes, from 2002 to 2021. 21,300 L-AH occurred throughout the year during 2002-2021. The incidence of hospitalization associated per 100,000 inhabitants by month showed a similar trend for the 2002-2011, 2012-2021, and 2002-2021 periods. In Spain, during 2002-2021, the hospitalization rate (HR) in the autonomous communities ranged from 4.57 (2002-2011) to 0.24 (2012-2021) cases per 100,000 inhabitants. The HR of legionellosis in Spain has substantially increased across the 2002-2021 period, and the estimate is consistent with available European data. It is considered that in-depth epidemiological surveillance studies of legionellosis and improvements in the prevention and control of the disease are required in Spain.
PubMed: 37512866
DOI: 10.3390/microorganisms11071693