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The Journal of Biological Chemistry Dec 2021Legionella pneumophila is a facultative intracellular pathogen that uses the Dot/Icm Type IV secretion system (T4SS) to translocate many effectors into its host and... (Review)
Review
Legionella pneumophila is a facultative intracellular pathogen that uses the Dot/Icm Type IV secretion system (T4SS) to translocate many effectors into its host and establish a safe, replicative lifestyle. The bacteria, once phagocytosed, reside in a vacuolar structure known as the Legionella-containing vacuole (LCV) within the host cells and rapidly subvert organelle trafficking events, block inflammatory responses, hijack the host ubiquitination system, and abolish apoptotic signaling. This arsenal of translocated effectors can manipulate the host factors in a multitude of different ways. These proteins also contribute to bacterial virulence by positively or negatively regulating the activity of one another. Such effector-effector interactions, direct and indirect, provide the delicate balance required to maintain cellular homeostasis while establishing itself within the host. This review summarizes the recent progress in our knowledge of the structure-function relationship and biochemical mechanisms of select effector pairs from Legionella that work in opposition to one another, while highlighting the diversity of biochemical means adopted by this intracellular pathogen to establish a replicative niche within host cells.
Topics: Animals; Bacterial Proteins; Homeostasis; Host-Pathogen Interactions; Humans; Inflammation; Legionella pneumophila; Legionnaires' Disease; Type IV Secretion Systems; Ubiquitination; Vacuoles
PubMed: 34695417
DOI: 10.1016/j.jbc.2021.101340 -
Annali Di Igiene : Medicina Preventiva... 2016The waterborne healthcare-associated infections are mainly sustained by Legionella and Pseudomonas spp. Various water factors and plumbing characteristics, and the... (Review)
Review
The waterborne healthcare-associated infections are mainly sustained by Legionella and Pseudomonas spp. Various water factors and plumbing characteristics, and the interaction with other water microorganisms are considered to be predictive of Legionella contamination. It is therefore mandatory to organize plans of surveillance, prevention and control in order to avoid disease appearance in immunosuppressed patients, with higher risk of death. Guidelines for the prevention of Legionnaires' disease have been published, benefiting those who face this problem, but definitive standardized solutions do not exist yet. Here we describe fifteen years of activity, during which our study group gathered interesting data on the control of Legionella contamination. Water disinfection is not generally sufficient to control the risk of infection, but a complex water safety plan should be developed, including system maintenance, training of staff and implementation of a clinical surveillance system aimed at early detection of cases. Concerning the control measures, we evaluated the effectiveness of different treatments suggested to reduce Legionella spp contamination, comparing our results with the current literature data. The performance ranking was highest for the filter, followed by boilers at high temperature, monochloramine and, at a lower level, chlorine dioxide; the effectiveness of hyperchlorination was limited, and thermal shock was even more ineffective.
Topics: Chloramines; Chlorine Compounds; Cross Infection; Disinfectants; Disinfection; Guidelines as Topic; Hospitals; Humans; Italy; Legionella; Legionnaires' Disease; Oxides; Population Surveillance
PubMed: 27071320
DOI: 10.7416/ai.2016.2088 -
Microbial Genomics Mar 2023are host-adapted bacteria that infect and reproduce primarily in amoeboid protists. Using similar infection mechanisms, they infect human macrophages, and cause...
are host-adapted bacteria that infect and reproduce primarily in amoeboid protists. Using similar infection mechanisms, they infect human macrophages, and cause Legionnaires' disease, an atypical pneumonia, and the milder Pontiac fever. We hypothesized that, despite the similarities in infection mechanisms, the hosts are different enough that there exist high-selective value mutations that would dramatically increase the fitness of inside the human host. By comparing a large number of isolates from independent infections, we identified two genes, mutated in three unrelated patients, despite the short duration of the incubation period (2-14 days). One is a gene coding for an outer membrane protein (OMP) belonging to the OmpP1/FadL family. The other is a gene coding for an EAL-domain-containing protein involved in cyclic-di-GMP regulation, which in turn modulates flagellar activity. The clinical strain, carrying the mutated EAL-domain-containing homologue, grows faster in macrophages than the wild-type strain, and thus appears to be better adapted to the human host. As human-to-human transmission is very rare, fixation of these mutations into the population and spread into the environment is unlikely. Therefore, parallel evolution - here mutations in the same genes observed in independent human infections - could point to adaptations to the accidental human host. These results suggest that despite the ability of to infect, replicate in and exit from macrophages, its human-specific adaptations are unlikely to be fixed in the population.
Topics: Humans; Legionella pneumophila; Legionella; Legionnaires' Disease; Macrophages
PubMed: 36947445
DOI: 10.1099/mgen.0.000958 -
BMC Infectious Diseases Sep 2023Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a β-lactam. However, the...
BACKGROUND
Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a β-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT).
METHODS
We conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a β-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality.
RESULTS
Among the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis.
CONCLUSION
Legionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia.
Topics: Humans; Anti-Bacterial Agents; Retrospective Studies; Pneumonia, Mycoplasma; Legionnaires' Disease; Lactams; Quinolones; Antigens, Bacterial; Community-Acquired Infections; Influenza, Human; beta-Lactams
PubMed: 37723456
DOI: 10.1186/s12879-023-08493-5 -
Frontiers in Public Health 2023pneumonia, rhabdomyolysis, and acute kidney injury are called the triad, which is rare and associated with a poor outcome and even death. Early diagnosis and timely...
Metagenomic next-generation sequencing confirms the diagnosis of pneumonia with rhabdomyolysis and acute kidney injury in a limited resource area: a case report and review.
BACKGROUND
pneumonia, rhabdomyolysis, and acute kidney injury are called the triad, which is rare and associated with a poor outcome and even death. Early diagnosis and timely treatment are essential for these patients.
CASE PRESENTATION
A 63-year-old man with cough, fever, and fatigue was initially misdiagnosed with common bacterial infection and given beta-lactam monotherapy but failed to respond to it. Conventional methods, including the first antibody test, sputum smear, and culture of sputum, blood, and bronchoalveolar lavage fluid (BALF) were negative. He was ultimately diagnosed with a severe infection of by metagenomics next-generation sequencing (mNGS). This patient, who had multisystem involvement and manifested with the rare triad of pneumonia, rhabdomyolysis, and acute kidney injury, finally improved after combined treatment with moxifloxacin, continuous renal replacement therapy, and liver protection therapy.
CONCLUSION
Our results showed the necessity of early diagnosis of pathogens in severe patients, especially in Legionnaires' disease, who manifested with the triad of pneumonia, rhabdomyolysis, and acute kidney injury. mNGS may be a useful tool for Legionnaires' disease in limited resource areas where urine antigen tests are not available.
Topics: Male; Humans; Middle Aged; Legionnaires' Disease; Acute Kidney Injury; Legionella; Rhabdomyolysis; Pneumonia; High-Throughput Nucleotide Sequencing
PubMed: 37228720
DOI: 10.3389/fpubh.2023.1145733 -
Annals of Agricultural and... Dec 2023Legionella bacteria are commonly found in natural aquatic environments such as rivers, lakes, ponds and hot springs. Legionella infection occurs through the inhalation...
INTRODUCTION AND OBJECTIVE
Legionella bacteria are commonly found in natural aquatic environments such as rivers, lakes, ponds and hot springs. Legionella infection occurs through the inhalation of water-air aerosol generated, for example, by showers or hot tubs. The most common species responsible for infection is Legionella pneumophila, which can cause Pontiac fever, and Legionnaires' disease, as well as a rare extrapulmonary form. The aim of the study's is to assess the susceptibility of Legionella pneumophila bacteria isolated from water systems of public buildings in Poland to antibiotics and chemotherapeutic agents used in the treatment of Legionellosis pneumonia.
MATERIAL AND METHODS
A total of 100 L. pneumophila strains isolated from public buildings, such as hospitals and water recreation facilities, were used for the study. The drug sensitivity of the following antibiotics was determined: erythromycin, azithromycin, ciprofloxacin, levofloxacin, rifampicin, trimethoprim-sulfamethoxazole and tetracycline. Mean MIC50 and MIC90 values were read using accepted standards.
RESULTS
The highest mean MIC value was obtained for tetracycline 6,130+/-0,353 μg/ml (with a range from 1,500 μg/ml to 16,000 μg/ml. In contrast, the lowest MIC was recorded with rifampicin: 0.020+/-0.037 μg/ml (with a range from 0.016 μg/ml to 0.380 μg/ml).
CONCLUSIONS
The lowest biocidal concentration was found for levofloxacin, the highest for tetracycline. The highest MIC50 and MIC90 values were found for tetracycline and the lowest for rifampicin. The highest biocidal values were found for azithromycin and the lowest for tetracycline.
Topics: Humans; Anti-Bacterial Agents; Legionella pneumophila; Rifampin; Levofloxacin; Azithromycin; Poland; Legionnaires' Disease; Tetracycline; Water; Legionella; Microbial Sensitivity Tests
PubMed: 38153060
DOI: 10.26444/aaem/167934 -
Bulletin of the World Health... 1990This Memorandum describes the following aspects of legionellosis: clinical presentations of legionella infection, general epidemiology (including nosocomial outbreaks... (Review)
Review
This Memorandum describes the following aspects of legionellosis: clinical presentations of legionella infection, general epidemiology (including nosocomial outbreaks and travel-associated legionnaires' disease), surveillance and reporting of cases, the organism and its environment, and measures for prevention and control. These topics were discussed by experts at a meeting in Geneva on 27-29 November 1989. This article also includes their conclusions and recommendations for research in critical areas including surveillance and preventive activities that have been found to be effective.
Topics: Cross Infection; Disease Outbreaks; Humans; Legionellosis; Legionnaires' Disease; Travel
PubMed: 2194686
DOI: No ID Found -
Scandinavian Journal of Work,... Jun 1999During a hot and humid summer period workers became ill with fever and flu-like symptoms after repairing a decanter for sludge concentration at a sewage treatment plant....
BACKGROUND AND OBJECTIVES
During a hot and humid summer period workers became ill with fever and flu-like symptoms after repairing a decanter for sludge concentration at a sewage treatment plant. The work took place over a period of 10 days in a small closed room, while another decanter was in operation and was consequently emitting aerosol to the environment, to which the workers were exposed. The aim of this study was to determine the cause of this outbreak of febrile illness so that additional cases could be prevented.
METHODS
All 5 patients were seen and examined in the Department of Occupational Medicine. Furthermore 2 of the workers had recurrent illness and were examined during hospitalization. As Pontiac fever (nonpneumonic legionellosis) was suspected, antibodies to legionellae were measured in blood samples. After positive antibody titers to Legionella pneumophila were found, samples of the sludge were collected for legionellae culture.
RESULTS AND CONCLUSIONS
The clinical picture agreed with that described for Pontiac fever, and positive antibody titers to L. pneumophila serogroup 1 were found in blood from all 5 patients. L. pneumophila serogroup 1 was cultured in high amounts from sludge from the decanter. It was concluded that the fever was caused by L. pneumophila emitted to the environment by the uncovered decanter. Procedures for preventing new cases were established.
Topics: Aerosols; Food Industry; Humans; Legionnaires' Disease; Occupational Diseases; Recurrence; Sewage; Waste Management
PubMed: 10450782
DOI: 10.5271/sjweh.437 -
Journal of Travel Medicine 2015Travel-associated Legionnaires' disease (LD) is a serious problem, and hundreds of cases are reported every year among travelers who stayed at hotels, despite the... (Review)
Review
BACKGROUND
Travel-associated Legionnaires' disease (LD) is a serious problem, and hundreds of cases are reported every year among travelers who stayed at hotels, despite the efforts of international and governmental authorities and hotel operators to prevent additional cases.
METHODS
A systematic review of travel-associated LD events (cases, clusters, outbreaks) and of environmental studies of Legionella contamination in accommodation sites was conducted. Two databases were searched (PubMed and EMBASE). Data were extracted from 50 peer-reviewed articles that provided microbiological and epidemiological evidence for linking the accommodation sites with LD. The strength of evidence was classified as strong, possible, and probable.
RESULTS
Three of the 21 hotel-associated events identified and four of nine ship-associated events occurred repeatedly on the same site. Of 197 hotel-associated cases, 158 (80.2%) were linked to hotel cooling towers and/or potable water systems. Ship-associated cases were most commonly linked to hot tubs (59/83, 71.1%). Common contributing factors included inadequate disinfection, maintenance, and monitoring; water stagnation; poor temperature control; and poor ventilation. Across all 30 events, Legionella concentrations in suspected water sources were >10,000 cfu/L, <10,000 cfu/L, and unknown in 11, 3, and 13 events, respectively. In five events, Legionella was not detected only after repeated disinfections. In environmental studies, Legionella was detected in 81.1% of ferries (23/28) and 48.9% of hotels (587/1,200), while all 12 cruise ships examined were negative.
CONCLUSIONS
This review highlights the need for LD awareness strategies targeting operators of accommodation sites. Increased standardization of LD investigation and reporting, and more rigorous follow-up of LD events, would help generate stronger, more comparable evidence on LD sources, contributing factors, and control measure effectiveness.
Topics: Disease Outbreaks; Humans; Legionella pneumophila; Legionnaires' Disease; Risk Factors; Ships; Travel
PubMed: 26220258
DOI: 10.1111/jtm.12225 -
Frontiers in Cellular and Infection... 2018is a gram-negative bacterium that inhabits freshwater ecosystems, where it is present in biofilm or as planktonic form. is mainly found associated with protozoa, which... (Review)
Review
is a gram-negative bacterium that inhabits freshwater ecosystems, where it is present in biofilm or as planktonic form. is mainly found associated with protozoa, which serve as protection from hostile environments and as replication niche. If inhaled within aerosols, is also able to infect and replicate in human alveolar macrophages, eventually causing the Legionnaires' disease. The transition between intracellular and extracellular environments triggers a differentiation program in which metabolic as well as morphogenetic changes occur. We here describe the current knowledge on how the different developmental states of this bacterium are regulated, with a particular emphasis on the stringent response activated during the transition from the replicative phase to the infectious phase and the metabolic features going in hand. We propose that the cellular differentiation of this intracellular pathogen is closely associated to key metabolic changes in the bacterium and the host cell, which together have a crucial role in the regulation of virulence.
Topics: Animals; Energy Metabolism; Environment; Host-Pathogen Interactions; Humans; Legionella pneumophila; Legionnaires' Disease; Life Cycle Stages; Metabolic Networks and Pathways; Virulence
PubMed: 29404281
DOI: 10.3389/fcimb.2018.00003