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1.
Front Cell Infect Microbiol ; 14: 1380312, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836055

RESUMO

Legionella, one of the main pathogens that causes community-acquired pneumonia, can lead to Legionella pneumonia, a condition characterized predominantly by severe pneumonia. This disease, caused by the bacterium Legionella pneumophila, can quickly progress to critical pneumonia and is often associated with damage to multiple organs. As a result, it requires close attention in terms of clinical diagnosis and treatment. Omadacycline, a new type of tetracycline derivative belonging to the aminomethylcycline class of antibiotics, is a semi-synthetic compound derived from minocycline. Its key structural feature, the aminomethyl modification, allows omadacycline to overcome bacterial resistance and broadens its range of effectiveness against bacteria. Clinical studies have demonstrated that omadacycline is not metabolized in the body, and patients with hepatic and renal dysfunction do not need to adjust their dosage. This paper reports a case of successful treatment of Legionella pneumonia with omadacycline in a patient who initially did not respond to empirical treatment with moxifloxacin. The patient also experienced electrolyte disturbance, as well as dysfunction in the liver and kidneys, delirium, and other related psychiatric symptoms.


Assuntos
Antibacterianos , Legionella pneumophila , Doença dos Legionários , Tetraciclinas , Humanos , Tetraciclinas/uso terapêutico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Doença dos Legionários/tratamento farmacológico , Doença dos Legionários/microbiologia , Legionella pneumophila/efeitos dos fármacos , Resultado do Tratamento , Masculino , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Moxifloxacina/uso terapêutico , Pessoa de Meia-Idade
2.
PLoS Pathog ; 20(5): e1011783, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38739652

RESUMO

Legionella pneumophila strains harboring wild-type rpsL such as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The bacterial factor directly responsible for inducing such cell death and the host factor involved in initiating the signaling cascade that leads to lysosome damage remain unknown. Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a and Nol9 as host factors important for restricting strain Lp02rpsLWT in BMDMs. Depletion of Hmg20a protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by Hmg20a was mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02rpsLWT in BMDMs. Our results establish that L. pneumophila exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.


Assuntos
Legionella pneumophila , Lisossomos , Macrófagos , Fagossomos , Proteínas rab de Ligação ao GTP , proteínas de unión al GTP Rab7 , Legionella pneumophila/metabolismo , Legionella pneumophila/genética , Animais , Proteínas rab de Ligação ao GTP/metabolismo , Camundongos , Fagossomos/metabolismo , Fagossomos/microbiologia , Lisossomos/metabolismo , Lisossomos/microbiologia , Macrófagos/microbiologia , Macrófagos/metabolismo , Doença dos Legionários/metabolismo , Doença dos Legionários/microbiologia , Sumoilação , Camundongos Endogâmicos C57BL , Endossomos/metabolismo , Endossomos/microbiologia
3.
J Assoc Physicians India ; 72(3): 94-96, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38736126

RESUMO

BACKGROUND: Legionella 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 Legionella. 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.


Assuntos
Azitromicina , Serosite , Humanos , Feminino , Serosite/diagnóstico , Serosite/etiologia , Azitromicina/uso terapêutico , Adulto , Antibacterianos/uso terapêutico , Legionelose/diagnóstico , Legionelose/tratamento farmacológico , Legionella/isolamento & purificação , Eletrocardiografia , Tomografia Computadorizada por Raios X , Doença dos Legionários/diagnóstico , Doença dos Legionários/tratamento farmacológico
4.
Int Immunopharmacol ; 134: 112254, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749333

RESUMO

BACKGROUND: Patients with diabetes are particularly susceptible to Legionella pneumophila (LP) infection, but the exact pathogenesis of LP infection in diabetic patients is still not fully understood. Herein, we investigated the effect of diabetes on immune function during LP infection in vitro and in vivo. METHODS: The time course of LP infection in macrophages under normal and high-glucose (HG) conditions was examined in vitro. Western blot was used to determine nucleotide-binding oligomerization domain 1 (NOD1), kinase 1/2 (ERK1/2), mitogen-activated protein kinase p38 (MAPK p38), and c-Jun N-terminal kinases (JNK). Enzyme-linked immunosorbent assay (ELISA) was used to assess the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Cell Counting Kit-8 (CCK8) assay assessed U937 cell viability after treating cells with different concentrations of high sugar medium and ML130 (NOD1 inhibitor). For the in vivo study, normal and streptozocin-induced diabetic guinea pigs were infected with LP for 6, 24, and 72 h, after which NOD1, MAPK-related signals, TNF-α, and IL-6 expression in lung tissues were assessed using immunohistochemistry, western blot, and RT-PCR. RESULTS: HG attenuated the upregulation of NOD1 expression and reduced TNF-α and IL-6 secretion caused by LP compared with LP-infected cells exposed to normal glucose levels (all p < 0.05). In diabetic guinea pigs, HG inhibited the upregulation of NOD1 expression in lung tissues and the activation of p38, ERK1/2, and cJNK caused by LP infection compared to control pigs (all p < 0.05). CONCLUSION: HG attenuates the response of macrophages to LP infection by inhibiting NOD1 upregulation and the activation of MAPK signaling.


Assuntos
Glucose , Legionella pneumophila , Macrófagos , Proteína Adaptadora de Sinalização NOD1 , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Adaptadora de Sinalização NOD1/genética , Animais , Humanos , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Legionella pneumophila/imunologia , Glucose/metabolismo , Cobaias , Masculino , Interleucina-6/metabolismo , Doença dos Legionários/imunologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células U937 , Fator de Necrose Tumoral alfa/metabolismo , Camundongos
5.
Euro Surveill ; 29(20)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38757288

RESUMO

Wastewater treatment plants (WWTPs) are increasingly identified as Legionnaires' disease (LD) sources. An outbreak investigation was initiated following five LD cases reported in September 2022 in Houten, the Netherlands. Case identification was based on the European LD case definition, with symptom onset from 1 September 2022, residence in or within 5 km of Houten, or visit to Houten within the incubation period, without other likely sources. We sampled potential sources and genotyped environmental and clinical isolates. We identified 15 LD cases with onset between 13 September and 23 October 2022. A spatial source identification and wind direction model suggested an industrial (iWWTP) and a municipal WWTP (mWWTP) as potential sources, with the first discharging water into the latter. Both tested positive for Legionella pneumophila serogroups 1 and 6 with multiple sequence types (ST). We detected L. pneumophila sg1 ST42 in the mWWTP, matching with one of three available clinical isolates. Following control measures at the WWTPs, no further cases were observed. This outbreak underlines that municipal and industrial WWTPs can play an important role in community LD cases and outbreaks, especially those with favourable conditions for Legionella growth and dissemination, or even non-favourable conditions for growth but with the influx of contaminated water.


Assuntos
Surtos de Doenças , Legionella pneumophila , Doença dos Legionários , Águas Residuárias , Microbiologia da Água , Doença dos Legionários/epidemiologia , Doença dos Legionários/microbiologia , Humanos , Países Baixos/epidemiologia , Águas Residuárias/microbiologia , Legionella pneumophila/isolamento & purificação , Legionella pneumophila/genética , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Purificação da Água , Adulto , Genótipo
6.
Emerg Infect Dis ; 30(5): 1022-1025, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38666647

RESUMO

We investigated molecular evolution and spatiotemporal dynamics of atypical Legionella pneumophila serogroup 1 sequence type 1905 and determined its long-term persistence and linkage to human disease in dispersed locations, far beyond the large 2014 outbreak epicenter in Portugal. Our finding highlights the need for public health interventions to prevent further disease spread.


Assuntos
Surtos de Doenças , Evolução Molecular , Legionella pneumophila , Doença dos Legionários , Análise Espaço-Temporal , Legionella pneumophila/genética , Legionella pneumophila/classificação , Portugal/epidemiologia , Humanos , Doença dos Legionários/epidemiologia , Doença dos Legionários/microbiologia , História do Século XXI , Recidiva , Filogenia , Sorogrupo
7.
J Infect Public Health ; 17(6): 1047-1049, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38678725

RESUMO

Legionellers' desease accounts for 1-8 % of cases of severe community-acquired pneumonia (CAP). Legionella spp. Is the causative organism that can result in respiratory failure, multi-organ dysfunction, sepsis, and death. Therefore, rapid diagnosis and efficient treatment are crucial. We report the clinical and microbiology study of a patient with community-acquired pneumonia caused by Legionella pneumophila, with fatal outcome. After death, the strain causing the infection was identified as Legionella pneumophila serogroup 1, Olda OLDA phenotype and sequence-type 1. This is the first reported case of septic shock and death associated with an isolate of these characteristics.


Assuntos
Infecções Comunitárias Adquiridas , Legionella pneumophila , Doença dos Legionários , Choque Séptico , Humanos , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/diagnóstico , Legionella pneumophila/isolamento & purificação , Legionella pneumophila/genética , Choque Séptico/microbiologia , Doença dos Legionários/diagnóstico , Doença dos Legionários/microbiologia , Evolução Fatal , Masculino , Idoso , Sorogrupo , Pessoa de Meia-Idade
8.
Cell Rep ; 43(4): 114033, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38568811

RESUMO

Small GTPases of the Ras subfamily are best known for their role as proto-oncoproteins, while their function during microbial infection has remained elusive. Here, we show that Legionella pneumophila hijacks the small GTPase NRas to the Legionella-containing vacuole (LCV) surface. A CRISPR interference screen identifies a single L. pneumophila effector, DenR (Lpg1909), required for this process. Recruitment is specific for NRas, while its homologs KRas and HRas are excluded from LCVs. The C-terminal hypervariable tail of NRas is sufficient for recruitment, and interference with either NRas farnesylation or S-acylation sites abrogates recruitment. Intriguingly, we detect markers of active NRas signaling on the LCV, suggesting it acts as a signaling platform. Subsequent phosphoproteomics analyses show that DenR rewires the host NRas signaling landscape, including dampening of the canonical mitogen-activated protein kinase pathway. These results provide evidence for L. pneumophila targeting NRas and suggest a link between NRas GTPase signaling and microbial infection.


Assuntos
Proteínas de Bactérias , GTP Fosfo-Hidrolases , Legionella pneumophila , Sistema de Sinalização das MAP Quinases , Proteínas de Membrana , Legionella pneumophila/metabolismo , Legionella pneumophila/patogenicidade , Humanos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Regulação para Baixo , Células HEK293 , Doença dos Legionários/microbiologia , Doença dos Legionários/metabolismo , Vacúolos/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética
9.
J Clin Microbiol ; 62(4): e0130523, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38511938

RESUMO

The unprecedented precision and resolution of whole genome sequencing (WGS) can provide definitive identification of infectious agents for epidemiological outbreak tracking. WGS approaches, however, are frequently impeded by low pathogen DNA recovery from available primary specimens or unculturable samples. A cost-effective hybrid capture assay for Legionella pneumophila WGS analysis directly on primary specimens was developed. DNA from a diverse range of sputum and autopsy specimens PCR-positive for L. pneumophila serogroup 1 (LPSG1) was enriched with this method, and WGS was performed. All tested specimens were determined to be enriched for Legionella reads (up to 209,000-fold), significantly improving the discriminatory power to compare relatedness when no clinical isolate was available. We found the WGS data from some enriched specimens to differ by less than five single-nucleotide polymorphisms (SNPs) when compared to the WGS data of a matched culture isolate. This testing and analysis retrospectively provided previously unconfirmed links to environmental sources for clinical specimens of sputum and autopsy lung tissue. The latter provided the additional information needed to identify the source of these culture-negative cases associated with the South Bronx 2015 Legionnaires' disease (LD) investigation in New York City. This new method provides a proof of concept for future direct clinical specimen hybrid capture enrichment combined with WGS and bioinformatic analysis during outbreak investigations.IMPORTANCELegionnaires' disease (LD) is a severe and potentially fatal type of pneumonia primarily caused by inhalation of Legionella-contaminated aerosols from man-made water or cooling systems. LD remains extremely underdiagnosed as it is an uncommon form of pneumonia and relies on clinicians including it in the differential and requesting specialized testing. Additionally, it is challenging to obtain clinical lower respiratory specimens from cases with LD, and when available, culture requires specialized media and growth conditions, which are not available in all microbiology laboratories. In the current study, a method for Legionella pneumophila using hybrid capture by RNA baiting was developed, which allowed us to generate sufficient genome resolution from L. pneumophila serogroup 1 PCR-positive clinical specimens. This new approach offers an additional tool for surveillance of future LD outbreaks where isolation of Legionella is not possible and may help solve previously unanswered questions from past LD investigations.


Assuntos
Legionella pneumophila , Legionella , Doença dos Legionários , Pneumonia , Humanos , Doença dos Legionários/diagnóstico , Estudos Retrospectivos , Legionella pneumophila/genética , Sequenciamento Completo do Genoma , Surtos de Doenças , DNA
10.
Ann Agric Environ Med ; 31(1): 24-28, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38549473

RESUMO

INTRODUCTION: Legionella pneumophila is the primary etiological agent of Legionnaires' disease. These are opportunistic pathogens causing lung infections by inhalation of contaminated aerosols. Controlling the presence of these bacteria in domestic distribution water systems (mainly hot water systems) is important for reducing the threat they pose to human health. Legionella pathogens are detected and quantified during routine testing of water samples according to procedures included in PN-EN ISO 11731:2017. However, these procedures are labour-intensive, and the results are obtained after a relatively long time. Implementing the Legiolert™/Quanti-Tray® test as an alternative method may constitute a good solution: it simplifies the testing procedure and significantly reduces the time necessary to obtain the final result. OBJECTIVE: The aim of the study was to compare the relative recovery of Legionella from water samples tested according to PN-EN ISO 11731:2017, and the alternative method of the most probable number (MPN) with the Legiolert™/Quanti-Tray® (IDEXX) test, and to assess the suitability of the alternative method for routine testing. MATERIAL AND METHODS: Parallel testing was conducted of 38 hot water samples to detect and determine Legionella acc. to PN-EN ISO 11731:2017 and the Legiolert™/Quanti-Tray® test. Statistical analysis of the results was performed according to PN-EN ISO 17994:2014 and the McNemar's test. RESULTS: The Legiolert™ test was confirmed to be comparable in performance to the reference standardized method in both qualitative and quantitative detection of L. pneumophila in hot water samples. CONCLUSIONS: The study confirmed that the Legiolert™ test is specific and easy to use, and may constitute an alternative to standardized procedures used in the quantification of L. pneumophila in water.


Assuntos
Água Potável , Legionella pneumophila , Legionella , Doença dos Legionários , Humanos , Microbiologia da Água , Aerossóis e Gotículas Respiratórios , Doença dos Legionários/diagnóstico , Doença dos Legionários/microbiologia
11.
Virulence ; 15(1): 2327096, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38466143

RESUMO

Legionella pneumophila (L. pneumophila) is a prevalent pathogenic bacterium responsible for significant global health concerns. Nonetheless, the precise pathogenic mechanisms of L. pneumophila have still remained elusive. Autophagy, a direct cellular response to L. pneumophila infection and other pathogens, involves the recognition and degradation of these invaders in lysosomes. Histone deacetylase 6 (HDAC6), a distinctive member of the histone deacetylase family, plays a multifaceted role in autophagy regulation. This study aimed to investigate the role of HDAC6 in macrophage autophagy via the autophagolysosomal pathway, leading to alleviate L. pneumophila-induced pneumonia. The results revealed a substantial upregulation of HDAC6 expression level in murine lung tissues infected by L. pneumophila. Notably, mice lacking HDAC6 exhibited a protective response against L. pneumophila-induced pulmonary tissue inflammation, which was characterized by the reduced bacterial load and diminished release of pro-inflammatory cytokines. Transcriptomic analysis has shed light on the regulatory role of HDAC6 in L. pneumophila infection in mice, particularly through the autophagy pathway of macrophages. Validation using L. pneumophila-induced macrophages from mice with HDAC6 gene knockout demonstrated a decrease in cellular bacterial load, activation of the autophagolysosomal pathway, and enhancement of cellular autophagic flux. In summary, the findings indicated that HDAC6 knockout could lead to the upregulation of p-ULK1 expression level, promoting the autophagy-lysosomal pathway, increasing autophagic flux, and ultimately strengthening the bactericidal capacity of macrophages. This contributes to the alleviation of L. pneumophila-induced pneumonia.


Assuntos
Legionella pneumophila , Legionella , Doença dos Legionários , Pneumonia , Animais , Camundongos , Autofagia , Desacetilase 6 de Histona/genética , Legionella pneumophila/genética , Doença dos Legionários/genética , Macrófagos
12.
J Occup Environ Hyg ; 21(4): 259-269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447033

RESUMO

Legionella pneumophila, the leading cause of Legionnaires' disease in the United States, is found in lakes, ponds, and streams but poses a health risk when it grows in building water systems. The growth of L. pneumophila in hot water systems of healthcare facilities poses a significant risk to patients, staff, and visitors. Hospitals and long-term care facilities account for 76% of reported Legionnaires' disease cases with mortality rates of 25%. Controlling L. pneumophila growth in hot water systems serving healthcare and hospitality buildings is currently achieved primarily by adding oxidizing chemical disinfectants. Chemical oxidants generate disinfection byproducts and can accelerate corrosion of premise plumbing materials and equipment. Alternative control methods that do not generate hazardous disinfection byproducts or accelerate corrosion are needed. L. pneumophila is an obligate aerobe that cannot sustain cellular respiration, amplify, or remain culturable when dissolved oxygen (DO) concentrations are too low (< 0.3 mg/L). An alternative method of controlling L. pneumophila growth by reducing DO levels in a hot water model system using a gas transfer membrane contactor was evaluated. A hot water model system was constructed and inoculated with L. pneumophila at DO concentrations above 0.5 mg/L. Once the model system was colonized, DO levels were incrementally reduced. Water samples were collected each week to evaluate the effect of reducing dissolved oxygen levels when all other conditions favored Legionella amplification. At DO concentrations below 0.3 mg/L, L. pneumophila concentrations were reduced by 1-log over 7 days. Under conditions in the hot water model system, at favorable temperatures and with no residual chlorine disinfectant, L. pneumophila concentrations were reduced by 1-log, indicating growth inhibition by reducing DO levels as the sole control measure. In sections of the model system where DO levels were not lowered L. pneumophila continued to grow. Reducing dissolved oxygen levels in hot water systems of healthcare and other large buildings to control L. pneumophila could also lower the risk of supplemental chemical treatment methods currently in use.


Assuntos
Desinfetantes , Legionella pneumophila , Legionella , Doença dos Legionários , Humanos , Doença dos Legionários/prevenção & controle , Abastecimento de Água , Engenharia Sanitária , Desinfetantes/farmacologia , Água/farmacologia , Microbiologia da Água , Temperatura Alta
13.
J Clin Microbiol ; 62(4): e0166523, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38501659

RESUMO

Many Legionella pneumonia patients do not produce sputum, and it is unknown whether purulent sputum is required for the identification of Legionella species. This study aimed to evaluate the identification rate of Legionella species based on sputum quality and the factors predictive of Legionella infection. This study included Legionella pneumonia patients at Kurashiki Central Hospital from November 2000 to December 2022. Sputum quality, based on gram staining, was classified as the following: Geckler 1/2, 3/6 and 4/5. Geckler 4/5 was defined as purulent sputum. The sputa of 104 of 124 Legionella pneumonia patients were cultured. Fifty-four patients (51.9%) were identified with Legionella species, most of which were Legionella pneumophila serogroup 1 (81.5%). The identification rates of Legionella species according to sputum quality were 57.1% (16/28) in Geckler 1/2 sputum, 50.0% (34/68) in Geckler 3/6 sputum, and 50.0% (4/8) in Geckler 4/5 sputum, which were not significantly different (P = 0.86). On multivariate analysis, pre-culture treatment with anti-Legionella antimicrobials (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.06-0.91), Pneumonia Severity Index class ≥IV (OR 2.57 [95% CI 1.02-6.71]), and intensive care unit admission (OR 3.08, 95% CI 1.06-10.09) correlated with the ability to identify Legionella species, but sputum quality did not (OR 0.88, 95% CI 0.17-4.41). The identification rate of Legionella species in non-purulent sputum was similar to that in purulent sputum. For the diagnosis of Legionella pneumonia, sputum should be collected before administering anti-Legionella antibiotics and cultured regardless of sputum quality.


Assuntos
Legionella pneumophila , Legionella , Doença dos Legionários , Pneumonia , Humanos , Escarro , Doença dos Legionários/diagnóstico
14.
Int J Infect Dis ; 142: 106965, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38367954

RESUMO

OBJECTIVES: The effectiveness of monotherapy and combination therapy with quinolones and macrolides for treating Legionnaires' disease remains uncertain; this study aimed to assess the comparative effectiveness of three treatment approaches. METHODS: Using a nationwide inpatient database, we analyzed 3560 eligible patients hospitalized for Legionnaires' disease between April 1, 2014, and March 31, 2021; patients were divided into combination therapy, quinolone monotherapy, and macrolide monotherapy groups according to the antibiotics administered within 2 days of admission. We compared in-hospital mortality, total hospitalization costs, and length of stay across these groups using multiple propensity score analysis with inverse probability of treatment weighting. RESULTS: Of the 3560 patients, there were 564 (15.8%), 2221 (62.4%), and 775 (21.8%) patients in the combination therapy, quinolone monotherapy, and macrolide monotherapy groups, respectively. No significant differences were observed in in-hospital mortality between combination therapy and quinolone monotherapy groups, and between combination therapy and macrolide monotherapy groups. There were no significant differences in total hospitalization costs or length of stay among the three groups. CONCLUSION: The study suggests that there may not be a significant advantage in using a combination of quinolones and macrolides over monotherapy for the treatment of Legionnaires' disease. Given the potential for increased side effects, careful consideration is advised when choosing this combination therapy.


Assuntos
Anti-Infecciosos , Doença dos Legionários , Quinolonas , Humanos , Doença dos Legionários/tratamento farmacológico , Pacientes Internados , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Macrolídeos/efeitos adversos , Quinolonas/uso terapêutico
15.
mBio ; 15(3): e0322123, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38335095

RESUMO

The survival of Legionella spp. as intracellular pathogens relies on the combined action of protein effectors delivered inside their eukaryotic hosts by the Dot/Icm (defective in organelle trafficking/intracellular multiplication) type IVb secretion system. The specific repertoire of effector arsenals varies dramatically across over 60 known species of this genera with Legionella pneumophila 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 Legionella species raising an intriguing question of their role in these bacteria's pathogenic strategy, which for most of these effectors remains unknown. L. pneumophila 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 Legionella hackeliae 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 in vitro 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 in vitro, revealing the potential function of VipF "core" effectors in Legionella's pathogenic strategy.IMPORTANCEBy translocating effectors inside the eukaryotic host cell, bacteria can modulate host cellular processes in their favor. Legionella species, which includes the pneumonia-causing Legionella pneumophila, 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 L. pneumophila 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 in vitro. These new data provide the first insight into the molecular function of this pathogenic factor family common across Legionellae.


Assuntos
Legionella pneumophila , Legionella , Doença dos Legionários , Humanos , Acetiltransferases/metabolismo , Fator de Iniciação 3 em Eucariotos/metabolismo , Lisina/metabolismo , Fator de Iniciação 3 em Procariotos/metabolismo , Legionella/genética , Legionella pneumophila/genética , Biossíntese de Proteínas , Proteínas de Bactérias/metabolismo
16.
Medicina (Kaunas) ; 60(2)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38399516

RESUMO

Background and Objectives: Legionnaires' disease (LD) is an acute respiratory disease with increasing annual numbers of reported domestic and global cases. This study aimed to establish foundational data for the prevention and control of LD by investigating the occurrence and infection routes of reported and suspected cases of LD in Gyeonggi Province, Korea, from January 2016 to December 2022, and by and analyzing the risk factors for death. Materials and Methods: A sex-and-age standardization was performed on LD patients and suspected cases reported in Gyeonggi Province. The monthly average number of confirmed cases was visualized using graphs, and a survival analysis was performed using Kaplan-Meier survival curves. The mortality risk ratio was estimated using the Cox proportional hazards model. Results: The incidence of LD in Gyeonggi Province mirrored the national trend, peaking in July with the highest number of confirmed and suspected cases. While there was no significant difference in survival rates by age, the survival rate was higher for suspected cases when analyzed separately. Comparing the death ratio by infection route, nosocomial infections showed the highest death ratio, and intensive care unit (ICU) admission and the presence of coinfections were significantly correlated with mortality. Factors such as nosocomial infection, admission within 1 to 3 days following diagnosis, and the development of complications were factors contributing to a higher risk of death. Conclusions: The general characteristics of patients with LD were similar to those suggested by previous studies. The proportion of community-acquired infections was lower than in previous studies, but the length of hospital stay was similar for survivors and the deceased, and the mortality rate within 30 days after diagnosis was higher for nosocomial infections. In conclusion, nosocomial infection, a period of up to 3 days from admission to diagnosis, and complications were significantly related to the mortality rate of LD.


Assuntos
Infecção Hospitalar , Legionella pneumophila , Doença dos Legionários , Humanos , Doença dos Legionários/epidemiologia , Doença dos Legionários/diagnóstico , Doença dos Legionários/prevenção & controle , Infecção Hospitalar/diagnóstico , Estudos Epidemiológicos , Fatores de Risco , República da Coreia/epidemiologia
18.
Occup Environ Med ; 81(3): 163-166, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38360725

RESUMO

BACKGROUND: Certain workers are at increased risk for acquiring Legionnaires' disease compared with other workers. This study aims to identify occupations at increased risk for acquiring Legionnaires' disease. METHODS: Using data from the US Centers for Disease Control and Prevention's Supplemental Legionnaires' Disease Surveillance System, this study identified Legionnaires' disease confirmed patients ≥16 years of age in 39 states with reported symptom onset during 2014-2016. Age-adjusted and sex-adjusted incidence rate ratios (IRR) stratified by occupation group were calculated by comparing Legionnaires' disease patients in an occupation group (eg, transportation) to those in all other occupation groups (eg, non-transportation). RESULTS: A total of 2553 patients had a known occupation group. The two occupations with the highest burden were transportation (N=287; IRR=2.11) and construction (N=269; IRR=1.82). Truck drivers comprised the majority (69.7%) of the transportation occupation group and construction labourers comprised almost half (49%) of the construction occupation group. The healthcare support occupation had the highest IRR (N=75; IRR=2.16). CONCLUSION: Transportation and construction workers, who are generally not covered by guidance related to building water systems, have increased risk of Legionnaires' disease compared with other workers. One hypothesised risk factor for truck drivers is the use of non-genuine windshield cleaner in their vehicles. A simple intervention is to use genuine windshield cleaner with bactericidal properties (ie, includes isopropanol/methanol) which can reduce the risk of Legionella growth and transmission. To improve surveillance of Legionnaires' disease and identification of similar exposures, the authors encourage the collection of occupation and industry information for all patients with Legionnaires' disease.


Assuntos
Doença dos Legionários , Humanos , Doença dos Legionários/diagnóstico , Doença dos Legionários/epidemiologia , Doença dos Legionários/etiologia , Ocupações , Fatores de Risco , Meios de Transporte , Indústrias , Surtos de Doenças
19.
Appl Environ Microbiol ; 90(3): e0129223, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38289130

RESUMO

Fundamental to effective Legionnaires' disease outbreak control is the ability to rapidly identify the environmental source(s) of the causative agent, Legionella pneumophila. Genomics has revolutionized pathogen surveillance, but L. pneumophila 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 L. pneumophila 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 L. pneumophila 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 Legionella pneumophila, 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 L. pneumophila 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.


Assuntos
Legionella pneumophila , Doença dos Legionários , Humanos , Legionella pneumophila/genética , Doença dos Legionários/epidemiologia , Tipagem de Sequências Multilocus/métodos , Genômica/métodos , Epidemiologia Molecular/métodos , Surtos de Doenças
20.
Epidemiol Infect ; 152: e18, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38204334

RESUMO

Legionellosis is a disease caused by the bacterium Legionella that most commonly presents as Legionnaires' disease (LD), a severe form of pneumonia. From 2015 to 2019, an average of 438 LD cases per year were reported in Canada. However, it is believed that the actual number of cases is much higher, since LD may be underdiagnosed and underreported. The purpose of this study was to develop an estimate of the true incidence of illnesses, hospitalizations, and deaths associated with LD in Canada. Values were derived using a stochastic model, based on Canadian surveillance data from 2015 to 2019, which were scaled up to account for underdiagnosis and underreporting. Overall, there were an estimated 1,113 (90% CrI: 737-1,730) illnesses, 1,008 (90% CrI: 271-2,244) hospitalizations, and 34 (90% CrI: 4-86) deaths due to domestically acquired waterborne LD annually in Canada from 2015 to 2019. It was further estimated that only 36% of illnesses and 39% of hospitalizations and deaths were captured in surveillance, and that 22% of illnesses were caused by Legionella serogroups and species other than Legionella pneumophila serogroup 1 (non-Lp1). This study highlights the true burden and areas for improvement in Canada's surveillance and detection of LD.


Assuntos
Legionella pneumophila , Legionella , Legionelose , Doença dos Legionários , Humanos , Doença dos Legionários/epidemiologia , Doença dos Legionários/microbiologia , Canadá/epidemiologia , Legionelose/epidemiologia , Legionelose/microbiologia , Efeitos Psicossociais da Doença
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