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Journal of Molecular Cell Biology Nov 2023Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease.... (Review)
Review
Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires' disease. During infections, L. pneumophila releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the host. Notably, certain effector proteins mediate posttranslational modifications (PTMs), serving as useful approaches exploited by L. pneumophila to modify host proteins. Some effectors catalyze the addition of host protein PTMs, while others mediate the removal of PTMs from host proteins. In this review, we summarize L. pneumophila effector-mediated PTMs of host proteins, including phosphorylation, ubiquitination, glycosylation, AMPylation, phosphocholination, methylation, and ADP-ribosylation, as well as dephosphorylation, deubiquitination, deAMPylation, deADP-ribosylation, dephosphocholination, and delipidation. We describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.
Topics: Humans; Legionella pneumophila; Legionnaires' Disease; Protein Processing, Post-Translational; Vacuoles; Ubiquitination
PubMed: 37156500
DOI: 10.1093/jmcb/mjad032 -
Annals of Intensive Care Apr 2024Legionnaires' disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and... (Review)
Review
BACKGROUND
Legionnaires' disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and advances in molecular testing have improved the diagnosis. LD entails intensive care unit (ICU) admission in almost one-third of cases, and the mortality rate ranges from 4% to 40%. This review aims to discuss recent advances in the study of this condition and to provide an update on the diagnosis, pathogenesis and management of severe LD.
RESULTS
The overall incidence of LD has increased worldwide in recent years due to the higher number of patients with risk factors, especially immunosuppression, and to improvements in diagnostic methods. Although LD is responsible for only around 5% of all-cause CAP, it is one of the three most common causes of CAP requiring ICU admission. Mortality in ICU patients, immunocompromised patients or patients with a nosocomial source of LD can reach 40% despite appropriate antimicrobial therapy. Regarding pathogenesis, no Legionella-specific virulence factors have been associated with severity; however, recent reports have found high pulmonary Legionella DNA loads, and impairments in immune response and lung microbiome in the most severe cases. The clinical picture includes severe lung injury requiring respiratory and/or hemodynamic support, extrapulmonary symptoms and non-specific laboratory findings. LD diagnostic methods have improved due to the broad use of UAT and the development of molecular methods allowing the detection of all Lp serogroups. Therapy is currently based on macrolides, quinolones, or a combination of the two, with prolonged treatment in severe cases.
CONCLUSIONS
Numerous factors influence the mortality rate of LD, such as ICU admission, the underlying immune status, and the nosocomial source of the infection. The host immune response (hyperinflammation and/or immunoparalysis) may also be associated with increased severity. Given that the incidence of LD is rising, studies on specific biomarkers of severity may be of great interest. Further assessments comparing different regimens and/or evaluating host-directed therapies are nowadays needed.
PubMed: 38565811
DOI: 10.1186/s13613-024-01252-y -
Epidemiology and Infection Jul 2023Over the past two decades, the incidence of legionellosis has been steadily increasing in the United States though there is noclear explanation for the main factors... (Review)
Review
Over the past two decades, the incidence of legionellosis has been steadily increasing in the United States though there is noclear explanation for the main factors driving the increase. While legionellosis is the leading cause of waterborne outbreaks in the US, most cases are sporadic and acquired in community settings where the environmental source is never identified. This scoping review aimed to summarise the drivers of infections in the USA and determine the magnitude of impact each potential driver may have. A total of 1,738 titles were screened, and 18 articles were identified that met the inclusion criteria. Strong evidence was found for precipitation as a major driver, and both temperature and relative humidity were found to be moderate drivers of incidence. Increased testing and improved diagnostic methods were classified as moderate drivers, and the ageing U.S. population was a minor driver of increasing incidence. Racial and socioeconomic inequities and water and housing infrastructure were found to be potential factors explaining the increasing incidence though they were largely understudied in the context of non-outbreak cases. Understanding the complex relationships between environmental, infrastructure, and population factors driving legionellosis incidence is important to optimise mitigation strategies and public policy.
Topics: United States; Humans; Incidence; Legionellosis; Disease Outbreaks; Temperature; Legionnaires' Disease
PubMed: 37503568
DOI: 10.1017/S0950268823001206 -
European Journal of Case Reports in... 2024Cytomegalovirus (CMV) infection is often asymptomatic. However, in certain individuals, it can cause non-specific signs and symptoms that maybe hard to recognise. The...
UNLABELLED
Cytomegalovirus (CMV) infection is often asymptomatic. However, in certain individuals, it can cause non-specific signs and symptoms that maybe hard to recognise. The condition may therefore be overlooked or misdiagnosed, leading to prolonged illness and serious sequelae. In this case report, we present a rare instance of CMV infection in an HIV-negative patient who had a remote history of splenectomy and was experiencing prolonged fever and markedly elevated white blood cell (WBC) count.
LEARNING POINTS
The clinical presentation of CMV infection in a post-splenectomy patient can be intricate and deceptive, involving non-specific symptoms such as prolonged fever and a markedly elevated WBC count.The decision on treatment among individuals without apparent risk factors (such as AIDS, transplant, or cancers) led to in-depth deliberations and discussion.Post-splenectomy patients with CMV infection may exhibit prolonged illness, potentially leading to severe consequences if left untreated.
PubMed: 38352817
DOI: 10.12890/2024_004263 -
Cureus Sep 2023A lung abscess is characterized as a clinical ailment arising from the localized suppurative necrosis of lung parenchyma. This condition primarily results from the...
A lung abscess is characterized as a clinical ailment arising from the localized suppurative necrosis of lung parenchyma. This condition primarily results from the complications of aspiration pneumonia due to anaerobic microorganisms originating from the oral cavity. Clinically, patients typically manifest symptoms such as fever, malaise, and a productive cough persisting over several weeks. The majority of lung abscess cases acquired within the community stem from anaerobic bacterial infections, often exhibiting a polymicrobial nature. We present a 51-year-old female with intrapulmonary abscess and empyema, with isolation of species. She has a 25-pack-year smoking history. Two weeks prior to arrival at our facility, she experienced intermittent shortness of breath, fever, and subjective fever. Her primary care physician ordered an outpatient computed tomography (CT) which showed evidence of a large right-sided fluid collection. Initial chest X-ray at our facility revealed extensive opacification of the middle and right lower hemithorax, believed to be a large-sized pleural effusion with adjacent pneumonia or atelectasis. She was given a working diagnosis of right-sided empyema. Cardiothoracic surgery was consulted and video-assisted thoracoscopic surgery (VATS) was performed. A very large collection of grossly purulent material was evacuated and revealed a large intrapulmonary abscess. Over 400 cc of frank pus was collected and sent for microbiological analysis. Anaerobic culture demonstrated 3+ species and 3+ species. The genus consists of a small, strictly anaerobic, gram-negative cocci that lacks flagella, spores, and capsules. This genus obtains energy from the utilization of short-chain organic acids that are present in the oral cavity and intestinal tract. Oral is strongly associated with biofilms, causing human oral infectious diseases such as periodontitis and dental caries. Literature states that this organism has been isolated in a limited number of chronic pneumonitis cases. To date, the most common organism isolated from lung abscesses is in adult patients and in pediatric patients. We strive to elucidate the distinctive clinical presentation evident in this case, alongside a comprehensive understanding of the unusual pathogens identified in the disease's pathogenesis.
PubMed: 37842426
DOI: 10.7759/cureus.45210 -
Frontiers in Microbiology 2023is an opportunistic intracellular pathogen that inhabits artificial water systems and can be transmitted to human hosts by contaminated aerosols. Upon inhalation, it... (Review)
Review
is an opportunistic intracellular pathogen that inhabits artificial water systems and can be transmitted to human hosts by contaminated aerosols. Upon inhalation, it colonizes and grows inside the alveolar macrophages and causes Legionnaires' disease. To effectively control and manage Legionnaires' disease, a deep understanding of the host-pathogen interaction is crucial. Bacterial extracellular vesicles, particularly outer membrane vesicles (OMVs) have emerged as mediators of intercellular communication between bacteria and host cells. These OMVs carry a diverse cargo, including proteins, toxins, virulence factors, and nucleic acids. OMVs play a pivotal role in disease pathogenesis by helping bacteria in colonization, delivering virulence factors into host cells, and modulating host immune responses. This review highlights the role of OMVs in the context of host-pathogen interaction shedding light on the pathogenesis of . Understanding the functions of OMVs and their cargo provides valuable insights into potential therapeutic targets and interventions for combating Legionnaires' disease.
PubMed: 37817751
DOI: 10.3389/fmicb.2023.1270123 -
Cell Reports Aug 2023Xenophagy is an evolutionarily conserved host defensive mechanism to eliminate invading microorganisms through autophagic machinery. The intracellular bacterial pathogen...
Xenophagy is an evolutionarily conserved host defensive mechanism to eliminate invading microorganisms through autophagic machinery. The intracellular bacterial pathogen Legionella pneumophila can avoid clearance by the xenophagy pathway via the actions of multiple Dot/Icm effector proteins. Previous studies have shown that p62, an adaptor protein involved in xenophagy signaling, is excluded from Legionella-containing vacuoles (LCVs). Such defects are attributed to the multifunctional SidE family effectors (SidEs) that exhibit classic deubiquitinase (DUB) and phosphoribosyl ubiquitination (PR-ubiquitination) activities, yet the mechanism remains elusive. In the present study, we demonstrate that the host DUB USP14 is PR-ubiquitinated by SidEs at multiple serine residues, which impairs its DUB activity and its interactions with p62. The exclusion of p62 from the bacterial phagosome requires the ubiquitin ligase but not the DUB activity of SidEs. These results reveal that PR-ubiquitination of USP14 by SidEs contributes to the evasion of xenophagic clearance by L. pneumophila.
Topics: Humans; Legionella; Legionnaires' Disease; Serine; Bacterial Proteins; Ubiquitination; Ubiquitin; Phagosomes; Vacuoles; Ubiquitin Thiolesterase
PubMed: 37471226
DOI: 10.1016/j.celrep.2023.112817 -
Microorganisms Jun 2023Legionellosis is a respiratory disease of bacterial and environmental origin that usually presents two distinct clinical entities, "Legionnaires' disease" (LD) and...
Legionellosis is a respiratory disease of bacterial and environmental origin that usually presents two distinct clinical entities, "Legionnaires' disease" (LD) and "Pontiac fever". LD is an important cause of hospital-acquired pneumonia (HAP). The objective of this study is to describe the epidemiology of legionellosis-associated hospitalization (L-AH) in Spain from 2002 to 2021 and the burden of hospitalization due to legionellosis. Discharge reports from the Minimum Basic Data Set (MBDS) were used to retrospectively analyze hospital discharge data with a diagnosis of legionellosis, based on the ICD-9-CM and ICD-10-CM diagnosis codes, from 2002 to 2021. 21,300 L-AH occurred throughout the year during 2002-2021. The incidence of hospitalization associated per 100,000 inhabitants by month showed a similar trend for the 2002-2011, 2012-2021, and 2002-2021 periods. In Spain, during 2002-2021, the hospitalization rate (HR) in the autonomous communities ranged from 4.57 (2002-2011) to 0.24 (2012-2021) cases per 100,000 inhabitants. The HR of legionellosis in Spain has substantially increased across the 2002-2021 period, and the estimate is consistent with available European data. It is considered that in-depth epidemiological surveillance studies of legionellosis and improvements in the prevention and control of the disease are required in Spain.
PubMed: 37512866
DOI: 10.3390/microorganisms11071693