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Clinical Infectious Diseases : An... Jun 2021
Topics: Anti-Bacterial Agents; Fluoroquinolones; Humans; Legionella; Legionnaires' Disease; Macrolides; Pneumonia
PubMed: 32296825
DOI: 10.1093/cid/ciaa442 -
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 -
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 -
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 -
BioTechniques Jun 2022
Topics: Bacteria; Drinking Water; Humans; Legionella; Legionnaires' Disease; Water Microbiology
PubMed: 35469440
DOI: 10.2144/btn-2022-0047 -
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 -
Applied and Environmental Microbiology Feb 2022Legionella pneumophila widely exists in natural and artificial water environments, which enables it to infect people. L. pneumophila infection causes Legionnaires'...
Legionella pneumophila widely exists in natural and artificial water environments, which enables it to infect people. L. pneumophila infection causes Legionnaires' disease (LD), which is a significant but relatively uncommon respiratory infection. Approximately 90% of LD is caused by L. pneumophila serogroup 1 (Lp1). Meteorological conditions may affect the infectivity and virulence of Lp1, but the exact relationship between them is still unclear. In this study, we evaluated the virulence of Lp1 by screening of total 156 Lp1 strains isolated from cooling tower water in different regions of China by detecting their abilities to activate NF-κB signaling pathway . In addition, we screened the distribution of some selected virulence genes in these strains. The virulence, virulence gene distribution, and the meteorological factors were analyzed. We found that both the virulence and the distribution of virulence genes had a certain regional and meteorological correlation. Although the loss of several virulence genes showed significant effects on the virulence of Lp1 strains, the distribution of virulence genes had very limited effects on the virulence of Lp1. LD is likely to be underrecognized in many countries. Due to the widespread existence of L. pneumophila in natural and artificial water environments and to the lack of cross-protection against different strains, L. pneumophila is a potentially serious threat to human health. Therefore, effective monitoring of the virulence of L. pneumophila in the water environment is very important to prevent and control the prevalence of LD. Understanding the virulence of L. pneumophila can not only help us to predict the risk of possible outbreaks in advance but can also enable more targeted clinical treatment. This study highlights the importance of understanding the epidemiology and ecology of L. pneumophila isolated from public facilities in terms of public health and biology. Due to the potential for water sources to harbor and disseminate L. pneumophila and to the fact that geographical conditions influence the virulence of L. pneumophila, timely and accurate L. pneumophila virulence surveillance is urgently needed.
Topics: China; Disease Outbreaks; Ecology; Humans; Legionella pneumophila; Legionnaires' Disease; Water Microbiology
PubMed: 34818106
DOI: 10.1128/AEM.01921-21