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Osong Public Health and Research... Aug 2023The number of reported cases of Legionnaires' disease (LD) in the Republic of Korea surged nationally in 2016; however, in 2022, this number was higher in Jeju Province...
BACKGROUND
The number of reported cases of Legionnaires' disease (LD) in the Republic of Korea surged nationally in 2016; however, in 2022, this number was higher in Jeju Province than the previous national peak. A descriptive epidemiological study was conducted to analyze trends in the incidence of reported LD cases in Jeju Island from 2015 to 2022.
METHODS
The data for this study were obtained from case reports submitted to the Korea Disease Control and Prevention Agency through its Disease and Health Integrated Management System. The selection criteria were cases or suspected cases of LD reported among Jeju residents between 2015 and 2022. The 95% confidence interval of the crude incidence rate was calculated using the Poisson distribution.
RESULTS
Since 2020, the incidence rate of LD in Jeju has risen sharply, showing a statistically significant difference from the national incidence rate. A particular medical institution in Jeju reported a significant number of LD cases. Screening with the urine antigen test (UAT) also increased significantly.
CONCLUSION
Our findings indicate that the rapid increase in cases of LD in Jeju Province since 2020 was due to the characteristics of medical-care use among Jeju residents, which were focused on a specific medical institution. According to their clinical practice guidelines, this medical institution conducted UATs to screen patients suspected of pneumonia.
PubMed: 37652687
DOI: 10.24171/j.phrp.2023.0145 -
Applied and Environmental Microbiology Mar 2024Fundamental to effective Legionnaires' disease outbreak control is the ability to rapidly identify the environmental source(s) of the causative agent, . Genomics has...
Fundamental to effective Legionnaires' disease outbreak control is the ability to rapidly identify the environmental source(s) of the causative agent, . Genomics has revolutionized pathogen surveillance, but has a complex ecology and population structure that can limit source inference based on standard core genome phylogenetics. Here, we present a powerful machine learning approach that assigns the geographical source of Legionnaires' disease outbreaks more accurately than current core genome comparisons. Models were developed upon 534 . genome sequences, including 149 genomes linked to 20 previously reported Legionnaires' disease outbreaks through detailed case investigations. Our classification models were developed in a cross-validation framework using only environmental genomes. Assignments of clinical isolate geographic origins demonstrated high predictive sensitivity and specificity of the models, with no false positives or false negatives for 13 out of 20 outbreak groups, despite the presence of within-outbreak polyclonal population structure. Analysis of the same 534-genome panel with a conventional phylogenomic tree and a core genome multi-locus sequence type allelic distance-based classification approach revealed that our machine learning method had the highest overall classification performance-agreement with epidemiological information. Our multivariate statistical learning approach maximizes the use of genomic variation data and is thus well-suited for supporting Legionnaires' disease outbreak investigations.IMPORTANCEIdentifying the sources of Legionnaires' disease outbreaks is crucial for effective control. Current genomic methods, while useful, often fall short due to the complex ecology and population structure of , the causative agent. Our study introduces a high-performing machine learning approach for more accurate geographical source attribution of Legionnaires' disease outbreaks. Developed using cross-validation on environmental genomes, our models demonstrate excellent predictive sensitivity and specificity. Importantly, this new approach outperforms traditional methods like phylogenomic trees and core genome multi-locus sequence typing, proving more efficient at leveraging genomic variation data to infer outbreak sources. Our machine learning algorithms, harnessing both core and accessory genomic variation, offer significant promise in public health settings. By enabling rapid and precise source identification in Legionnaires' disease outbreaks, such approaches have the potential to expedite intervention efforts and curtail disease transmission.
Topics: Humans; Legionella pneumophila; Legionnaires' Disease; Multilocus Sequence Typing; Genomics; Molecular Epidemiology; Disease Outbreaks
PubMed: 38289130
DOI: 10.1128/aem.01292-23 -
Current Microbiology May 2024Legionella pneumophila (Lp) is a Gram-negative bacterium found in natural and artificial aquatic environments and inhalation of contaminated aerosols can cause severe...
Legionella pneumophila (Lp) is a Gram-negative bacterium found in natural and artificial aquatic environments and inhalation of contaminated aerosols can cause severe pneumonia known as Legionnaires' Disease (LD). In Brazil there is hardly any information about this pathogen, so we studied the genetic variation of forty Legionella spp. isolates obtained from hotels, malls, laboratories, retail centers, and companies after culturing in BCYE medium. These isolates were collected from various sources in nine Brazilian states. Molecular identification of the samples was carried out using Sequence-Based Typing (SBT), which consists of sequencing and analysis of seven genes (flaA, pilE, asd, mip, mompS, proA, and neuA) to define a Sequence Type (ST). Eleven STs were identified among 34/40 isolates, of which eight have been previously described (ST1, ST80, ST152, ST242, ST664, ST1185, ST1464, ST1642) and three were new STs (ST2960, ST2962, and ST2963), the former identified in five different cooling towers in the city of São Paulo. The ST1 that is widely distributed in many countries was also the most prevalent in this study. In addition, other STs that we observed have also been associated with legionellosis in other countries, reinforcing the potential of these isolates to cause LD in Brazil. Unfortunately, no human isolates could be characterized until presently, but our observations strongly suggest the need of surveillance implementation system and control measures of Legionella spp. in Brazil, including the use of more sensitive genotyping procedures besides ST.
Topics: Brazil; Legionella pneumophila; Genetic Variation; Water Microbiology; Humans; Phylogeny; Genotype
PubMed: 38714565
DOI: 10.1007/s00284-024-03645-5 -
Infection and Immunity Jan 2024is a common intracellular parasitic bacterium that infects humans via the respiratory tract, causing Legionnaires' disease, with fever and pneumonia as the main...
is a common intracellular parasitic bacterium that infects humans via the respiratory tract, causing Legionnaires' disease, with fever and pneumonia as the main symptoms. The emergence of highly virulent and azithromycin-resistant is a major challenge in clinical anti-infective therapy. The CRISPR-Cas acquired immune system provides immune defense against foreign nucleic acids and regulates strain biological functions. However, the distribution of the CRISPR-Cas system in and how it regulates gene expression in remain unclear. Herein, we assessed 915 whole-genome sequences to determine the distribution characteristics of the CRISPR-Cas system and constructed gene deletion mutants to explore the regulation of the system based on growth ability , antibiotic sensitivity, and intracellular proliferation of . The CRISPR-Cas system in was predominantly Type II-B and was mainly concentrated in the genome of ST1 strains. The Type II-B CRISPR-Cas system showed no effect on the strain's growth ability but significantly reduced resistance to azithromycin and decreased proliferation ability due to regulation of the efflux pump and the Dot/Icm type IV secretion system. Thus, the Type II-B CRISPR-Cas system plays a crucial role in regulating the virulence of . This expands our understanding of drug resistance and pathogenicity in , provides a scientific basis for the prevention of Legionnaires' disease outbreaks and the rational use of clinical drugs, and facilitates effective treatment of Legionnaires' disease.
Topics: Humans; Legionnaires' Disease; Legionella; Azithromycin; CRISPR-Cas Systems; Legionella pneumophila
PubMed: 38099659
DOI: 10.1128/iai.00229-23 -
Microorganisms Jul 2023contamination control is crucial in healthcare settings where patients suffer an increased risk of disease and fatal outcome. To ensure an effective management of this...
Water Safety Plan, Monochloramine Disinfection and Extensive Environmental Sampling Effectively Control and Other Waterborne Pathogens in Nosocomial Settings: The Ten-Year Experience of an Italian Hospital.
contamination control is crucial in healthcare settings where patients suffer an increased risk of disease and fatal outcome. To ensure an effective management of this health hazard, the accurate application of a hospital-specific Water Safety Plan (WSP), the choice of a suitable water disinfection system and an extensive monitoring program are required. Here, the ten-year experience of an Italian hospital is reported: since its commissioning, Legionellosis risk management has been entrusted to a multi-disciplinary Working Group, applying the principles of the World Health Organization's WSP. The disinfection strategy to prevent and other waterborne pathogens relies on the treatment of domestic hot water with a system ensuring the in situ production and dosage of monochloramine. An average of 250 samples/year were collected and analyzed to allow an accurate assessment of the microbiological status of water network. With the aim of increasing the monitoring sensitivity, in addition to the standard culture method, an optimized MALDI-ToF MS-based strategy was applied, allowing the identification of species and other relevant opportunistic pathogens. Data collected so far confirmed the effectiveness of this multidisciplinary approach: the fraction of positive samples never overcame 1% on a yearly basis and Legionnaires' Disease cases never occurred.
PubMed: 37512966
DOI: 10.3390/microorganisms11071794 -
MBio Mar 2024The survival of spp. as intracellular pathogens relies on the combined action of protein effectors delivered inside their eukaryotic hosts by the Dot/Icm (efective in...
The survival of spp. as intracellular pathogens relies on the combined action of protein effectors delivered inside their eukaryotic hosts by the Dot/Icm (efective in rganelle rafficking/ntraellular ultiplication) type IVb secretion system. The specific repertoire of effector arsenals varies dramatically across over 60 known species of this genera with responsible for most cases of Legionnaires' disease in humans encoding over 360 Dot/Icm effectors. However, a small subset of "core" effectors appears to be conserved across all species raising an intriguing question of their role in these bacteria's pathogenic strategy, which for most of these effectors remains unknown. Lpg0103 effector, also known as VipF, represents one of the core effector families that features a tandem of Gcn5-related N-acetyltransferase (GNAT) domains. Here, we present the crystal structure of the Lha0223, the VipF representative from in complex with acetyl-coenzyme A determined to 1.75 Å resolution. Our structural analysis suggested that this effector family shares a common fold with the two GNAT domains forming a deep groove occupied by residues conserved across VipF homologs. Further analysis suggested that only the C-terminal GNAT domain of VipF effectors retains the active site composition compatible with catalysis, whereas the N-terminal GNAT domain binds the ligand in a non-catalytical mode. We confirmed this by enzymatic assays which revealed VipF activity not only against generic small molecule substrates, such as chloramphenicol, but also against poly-L-lysine and histone-derived peptides. We identified the human eukaryotic translation initiation factor 3 (eIF3) complex co-precipitating with Lpg0103 and demonstrated the direct interaction between the several representatives of the VipF family, including Lpg0103 and Lha0223 with the K subunit of eIF3. According to our data, these interactions involve primarily the C-terminal tail of eIF3-K containing two lysine residues that are acetylated by VipF. VipF catalytic activity results in the suppression of eukaryotic protein translation , revealing the potential function of VipF "core" effectors in 's pathogenic strategy.IMPORTANCEBy translocating effectors inside the eukaryotic host cell, bacteria can modulate host cellular processes in their favor. species, which includes the pneumonia-causing encode a widely diverse set of effectors with only a small subset that is conserved across this genus. Here, we demonstrate that one of these conserved effector families, represented by VipF (Lpg0103), is a tandem Gcn5-related N-acetyltransferase interacting with the K subunit of human eukaryotic initiation factor 3 complex. VipF catalyzes the acetylation of lysine residues on the C-terminal tail of the K subunit, resulting in the suppression of eukaryotic translation initiation factor 3-mediated protein translation . These new data provide the first insight into the molecular function of this pathogenic factor family common across .
Topics: Humans; Acetyltransferases; Eukaryotic Initiation Factor-3; Lysine; Prokaryotic Initiation Factor-3; Legionella; Legionella pneumophila; Legionnaires' Disease; Protein Biosynthesis; Bacterial Proteins
PubMed: 38335095
DOI: 10.1128/mbio.03221-23 -
Cureus Aug 2023Lemierre's syndrome, also known as anaerobic post-anginal septicemia, necrobacillosis, and the "forgotten disease," is a rare manifestation. It is often presented with...
Lemierre's syndrome, also known as anaerobic post-anginal septicemia, necrobacillosis, and the "forgotten disease," is a rare manifestation. It is often presented with sepsis, sore throat, fever, neck pain, internal jugular vein thrombophlebitis/thrombosis, and septic emboli. The bacteria that are usually associated with the disease are species, but it is also associated with , , and other bacterial species. The diagnosis of Lemierre's syndrome is made based on evidence of septic thrombophlebitis, preceding oropharyngeal infection, and positive culture. Treatment usually consists of antibiotics directed toward the causative organism. The use of anticoagulation, although controversial, is shown to be beneficial by several studies. We describe a middle-aged patient who presented with a sore throat, neck pain, and dysphagia. Imaging of the neck and chest revealed right jugular thrombosis along with septic emboli in the lungs. The culture of the blood and pus drained from the peritonsillar abscess grew . In this study, we have illustrated the effective management of Lemierre's syndrome with antibiotics, anticoagulants, and needle aspiration of abscess.
PubMed: 37779762
DOI: 10.7759/cureus.44311 -
MBio Oct 2023Before environmental opportunistic pathogens can infect humans, they must first successfully grow and compete with other microbes in nature, often via secreted...
Before environmental opportunistic pathogens can infect humans, they must first successfully grow and compete with other microbes in nature, often via secreted antimicrobials. We previously discovered that the bacterium , the causative agent of Legionnaires' disease, can compete with other microbes via a secreted molecule called HGA. Curiously, strains that produce HGA is not wholly immune to its toxicity, making it a mystery how these bacteria can withstand the "friendly fire" of potentially self-targeting antimicrobials during inter-bacterial battles. Here, we identify several strategies that allow the high-density bacterial populations that secrete HGA to tolerate its effects. Our study clarifies how HGA works. It also points to some explanations of why it is difficult to disinfect from the built environment and prevent disease outbreaks.
Topics: Humans; Legionella pneumophila; Legionnaires' Disease
PubMed: 37728338
DOI: 10.1128/mbio.01207-23 -
Metabolites Jul 2023() is a common etiological agent of bacterial pneumonia that causes Legionnaires' disease (LD). The bacterial membrane-associated virulence factor macrophage...
() is a common etiological agent of bacterial pneumonia that causes Legionnaires' disease (LD). The bacterial membrane-associated virulence factor macrophage infectivity potentiator (Mip) exhibits peptidyl-prolyl--isomerase (PPIase) activity and contributes to the intra- and extracellular pathogenicity of . Though Mip influences disease outcome, little is known about the metabolic consequences of altered Mip activity during infections. Here, we established a metabolic workflow and applied mass spectrometry approaches to decipher how Mip activity influences metabolism and pathogenicity. Impaired Mip activity in genetically engineered strains decreases intracellular replication in cellular infection assays, confirming the contribution of Mip for pathogenicity. We observed that genetic and chemical alteration of Mip using the PPIase inhibitors rapamycin and FK506 induces metabolic reprogramming in , specifically branched-chain amino acid (BCAA) metabolism. Rapamycin also inhibits PPIase activity of mammalian FK506 binding proteins, and we observed that rapamycin induces a distinct metabolic signature in human macrophages compared to bacteria, suggesting potential involvement of Mip in normal bacteria and in infection. Our metabolic studies link Mip to alterations in BCAA metabolism and may help to decipher novel disease mechanisms associated with LD.
PubMed: 37512541
DOI: 10.3390/metabo13070834 -
International Journal of Environmental... Sep 2023Travel-associated Legionnaires' disease is a significant public health concern worldwide. A high number of cases are reported every year among travellers who stay at...
Travel-associated Legionnaires' disease is a significant public health concern worldwide. A high number of cases are reported every year among travellers who stay at guest houses, hotels, and spas. Indeed, hot water systems, showers, and air-conditioning systems can be contaminated by , which grows at 25-42 °C. Studies have shown that in Sardinia, especially during the summer months, the water circulation in the hotels' pipes is exposed to extremely high temperatures. As a result, this study was conducted to assess the colonization of hotel water systems by in Sardinia, concerning a recent EU directive 2020/2184 for drinking water with a limit of 1000 CFU /L. Methods. A total of 112 accommodation facilities were analyzed, of which 61.3% were found to be colonized with , and out of a total of 807 samples, 32.5% were positive for presence. The results showed a higher number of positive samples in the summer season. This was also associated with the higher concentration presence of >1000 CFU/L in the samples. Consequently, this study confirms that local hotel operators should improve their water safety and prevention plans, especially in spring and summer.
PubMed: 37754582
DOI: 10.3390/ijerph20186722