-
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 -
Respiratory Investigation Mar 2024
Topics: Humans; Legionella; Legionnaires' Disease; Legionella pneumophila
PubMed: 38301531
DOI: 10.1016/j.resinv.2024.01.008 -
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 -
Molecular Microbiology Aug 2023Lipid droplets (LDs) are dynamic and versatile organelles present in most eukaryotic cells. LDs consist of a hydrophobic core of neutral lipids, a phospholipid monolayer... (Review)
Review
Lipid droplets (LDs) are dynamic and versatile organelles present in most eukaryotic cells. LDs consist of a hydrophobic core of neutral lipids, a phospholipid monolayer coat, and a variety of associated proteins. LDs are formed at the endoplasmic reticulum and have diverse roles in lipid storage, energy metabolism, membrane trafficking, and cellular signaling. In addition to their physiological cellular functions, LDs have been implicated in the pathogenesis of several diseases, including metabolic disorders, cancer, and infections. A number of intracellular bacterial pathogens modulate and/or interact with LDs during host cell infection. Members of the genera Mycobacterium, Legionella, Coxiella, Chlamydia, and Salmonella exploit LDs as a source of intracellular nutrients and membrane components to establish their distinct intracellular replicative niches. In this review, we focus on the biogenesis, interactions, and functions of LDs, as well as on their role in lipid metabolism of intracellular bacterial pathogens.
Topics: Lipid Droplets; Diet; Lipid Metabolism
PubMed: 37429596
DOI: 10.1111/mmi.15120 -
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 -
Molecular Microbiology Feb 2024Legionella pneumophila is a gram-negative bacteria found in natural and anthropogenic aquatic environments such as evaporative cooling towers, where it reproduces as an... (Review)
Review
Legionella pneumophila is a gram-negative bacteria found in natural and anthropogenic aquatic environments such as evaporative cooling towers, where it reproduces as an intracellular parasite of cohabiting protozoa. If L. pneumophila is aerosolized and inhaled by a susceptible person, bacteria may colonize their alveolar macrophages causing the opportunistic pneumonia Legionnaires' disease. L. pneumophila utilizes an elaborate regulatory network to control virulence processes such as the Dot/Icm Type IV secretion system and effector repertoire, responding to changing nutritional cues as their host becomes depleted. The bacteria subsequently differentiate to a transmissive state that can survive in the environment until a replacement host is encountered and colonized. In this review, we discuss the lifecycle of L. pneumophila and the molecular regulatory network that senses nutritional depletion via the stringent response, a link to stationary phase-like metabolic changes via alternative sigma factors, and two-component systems that are homologous to stress sensors in other pathogens, to regulate differentiation between the intracellular replicative phase and more transmissible states. Together, we highlight how this prototypic intracellular pathogen offers enormous potential in understanding how molecular mechanisms enable intracellular parasitism and pathogenicity.
Topics: Humans; Legionella pneumophila; Virulence; Sigma Factor; Bacterial Proteins
PubMed: 37908155
DOI: 10.1111/mmi.15172 -
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