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American Journal of Respiratory Cell... May 2021TOLLIP (Toll-interacting protein) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type-specific manner, TOLLIP can... (Review)
Review
TOLLIP (Toll-interacting protein) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type-specific manner, TOLLIP can function as an inhibitor of inflammation and endoplasmic-reticulum stress, an activator of autophagy, or a critical regulator of intracellular vacuole trafficking. The distinct functions of this protein have been linked to innate immune responses and lung epithelial-cell apoptosis. genetic variants have been associated with a variety of chronic lung diseases, including idiopathic pulmonary fibrosis, asthma, and primary graft dysfunction after lung transplantation, and with infections, such as tuberculosis, pneumonia, and respiratory viruses. TOLLIP exists in a delicate homeostatic balance, with both positive and negative effects on the trajectory of pulmonary diseases. This translational review summarizes the genetic and molecular associations that link TOLLIP to the development and progression of noninfectious and infectious pulmonary diseases. We highlight current limitations of and models in assessing the role of TOLLIP in these conditions, and we describe future approaches that will enable a more nuanced exploration of the role of TOLLIP in pulmonary conditions. There has been a surge in recent research evaluating the role of this protein in human diseases, but critical mechanistic pathways require further exploration. By understanding its biologic functions in disease-specific contexts, we will be able to determine whether TOLLIP can be therapeutically modulated to treat pulmonary diseases.
Topics: Animals; Asthma; Cytokines; Disease Models, Animal; Gene Expression Regulation; Graft Rejection; Humans; Idiopathic Pulmonary Fibrosis; Immunity, Innate; Intracellular Signaling Peptides and Proteins; Legionnaires' Disease; Lung Transplantation; Mice; MicroRNAs; Respirovirus Infections; Signal Transduction; Tuberculosis, Pulmonary
PubMed: 33233920
DOI: 10.1165/rcmb.2020-0470TR -
Pneumonia (Nathan Qld.) Jan 2021Due to similarities in initial disease presentation, clinicians may be inclined to repeatedly test community-acquired pneumonia cases for COVID-19 before recognizing the...
Due to similarities in initial disease presentation, clinicians may be inclined to repeatedly test community-acquired pneumonia cases for COVID-19 before recognizing the need to test for Legionnaires' disease. Legionnaires' disease is an illness characterized by pneumonia that has a summer/early fall seasonality due to favorable conditions for Legionella growth and exposure. Legionella proliferate in warm water environments and stagnant sections of indoor plumbing and cooling systems. During the ongoing pandemic crisis, exposures to aerosolized water from recently reopened office or retail buildings should be considered as an epidemiologic risk factor for Legionella exposure and an indication to test. The majority of Legionnaires' disease cases occurring each year are not diagnosed, and some experts recommend that all patients hospitalized with community-acquired pneumonia without a known etiology be tested for Legionella infection. Proper diagnosis can increase the likelihood of appropriate and timely antibiotic treatment, identify potential clusters of disease, and facilitate source attribution.
PubMed: 33407911
DOI: 10.1186/s41479-020-00080-5 -
ELife May 2023The amoeba-resistant bacterium causes Legionnaires' disease and employs a type IV secretion system (T4SS) to replicate in the unique, ER-associated -containing vacuole...
The amoeba-resistant bacterium causes Legionnaires' disease and employs a type IV secretion system (T4SS) to replicate in the unique, ER-associated -containing vacuole (LCV). The large fusion GTPase Sey1/atlastin is implicated in ER dynamics, ER-derived lipid droplet (LD) formation, and LCV maturation. Here, we employ cryo-electron tomography, confocal microscopy, proteomics, and isotopologue profiling to analyze LCV-LD interactions in the genetically tractable amoeba . Dually fluorescence-labeled producing LCV and LD markers revealed that Sey1 as well as the T4SS and the Ran GTPase activator LegG1 promote LCV-LD interactions. In vitro reconstitution using purified LCVs and LDs from parental or Δ mutant indicated that Sey1 and GTP promote this process. Sey1 and the fatty acid transporter FadL were implicated in palmitate catabolism and palmitate-dependent intracellular growth. Taken together, our results reveal that Sey1 and LegG1 mediate LD- and FadL-dependent fatty acid metabolism of intracellular .
Topics: Humans; Legionella pneumophila; GTP Phosphohydrolases; Macrophages; Dictyostelium; Lipid Droplets; Vacuoles; Legionella; Legionnaires' Disease; Bacterial Proteins
PubMed: 37158597
DOI: 10.7554/eLife.85142 -
Frontiers in Cellular and Infection... 2023The pathogenicity of , the causative agent of Legionnaires' disease, depends on an arsenal of interacting proteins. Here we describe how surface-associated and secreted... (Review)
Review
The pathogenicity of , the causative agent of Legionnaires' disease, depends on an arsenal of interacting proteins. Here we describe how surface-associated and secreted virulence factors of this pathogen interact with each other or target extra- and intracellular host proteins resulting in host cell manipulation and tissue colonization. Since progress of computational methods like AlphaFold, molecular dynamics simulation, and docking allows to predict, analyze and evaluate experimental proteomic and interactomic data, we describe how the combination of these approaches generated new insights into the multifaceted "protein sociology" of the zinc metalloprotease ProA and the peptidyl-prolyl isomerase Mip (macrophage infectivity potentiator). Both virulence factors of interact with numerous proteins including bacterial flagellin (FlaA) and host collagen, and play important roles in virulence regulation, host tissue degradation and immune evasion. The recent progress in protein-ligand analyses of virulence factors suggests that machine learning will also have a beneficial impact in early stages of drug discovery.
Topics: Humans; Legionella pneumophila; Bacterial Proteins; Virulence Factors; Proteomics; Peptidylprolyl Isomerase; Legionnaires' Disease
PubMed: 36936764
DOI: 10.3389/fcimb.2023.1140688 -
Emerging Infectious Diseases Mar 2022Reported Legionnaires' disease (LD) cases began increasing in the United States in 2003 after relatively stable numbers for >10 years; reasons for the rise are unclear.... (Review)
Review
Reported Legionnaires' disease (LD) cases began increasing in the United States in 2003 after relatively stable numbers for >10 years; reasons for the rise are unclear. We compared epidemiologic patterns associated with cases reported to the Centers for Disease Control and Prevention before and during the rise. The age-standardized average incidence was 0.48 cases/100,000 population during 1992-2002 compared with 2.71 cases/100,000 in 2018. Reported LD incidence increased in nearly every demographic, but increases tended to be larger in demographic groups with higher incidence. During both periods, the largest number of cases occurred among White persons, but the highest incidence was in Black or African American persons. Incidence and increases in incidence were generally largest in the East North Central, Middle Atlantic, and New England divisions. Seasonality was more pronounced during 2003-2018, especially in the Northeast and Midwest. Rising incidence was most notably associated with increasing racial disparities, geographic focus, and seasonality.
Topics: Centers for Disease Control and Prevention, U.S.; Humans; Incidence; Legionnaires' Disease; New England; United States
PubMed: 35195513
DOI: 10.3201/eid2803.211435 -
BioMed Research International 2022is found in the natural aquatic environment and can resist a wide range of environmental conditions. There are around fifty species of Legionella, at least twenty-four...
is found in the natural aquatic environment and can resist a wide range of environmental conditions. There are around fifty species of Legionella, at least twenty-four of which are directly linked to infections in humans. is the cause of Legionnaires' disease, a potentially lethal form of pneumonia. By blocking phagosome-lysosome fusion, lives and proliferates inside macrophages. For this disease, there is presently no authorized multiepitope vaccine available. For the multi-epitope-based vaccine (MEBV), the best antigenic candidates were identified using immunoinformatics and subtractive proteomic techniques. Several immunoinformatics methods were utilized to predict B and T cell epitopes from vaccine candidate proteins. To construct an vaccine, epitopes (07 CTL, 03 HTL, and 07 LBL) were carefully selected and docked with MHC molecules (MHC-I and MHC-II) and human TLR4 molecules. To increase the immunological response, the vaccine was combined with a 50S ribosomal adjuvant. To maximize vaccine protein expression, MEBV was cloned and reverse-translated in . To prove the MEBV's efficacy, more experimental validation is required. After its development, the resulting vaccine is greatly hoped to aid in the prevention of infections.
Topics: Bacterial Vaccines; Epitopes, T-Lymphocyte; Humans; Legionella pneumophila; Legionnaires' Disease; Proteomics; Toll-Like Receptor 4
PubMed: 36164443
DOI: 10.1155/2022/4975721 -
Pathogens (Basel, Switzerland) Apr 2020is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires' disease (LD) and Pontiac fever and is ubiquitous in... (Review)
Review
is an opportunistic waterborne pathogen of public health concern. It is the causative agent of Legionnaires' disease (LD) and Pontiac fever and is ubiquitous in manufactured water systems, where protozoan hosts and complex microbial communities provide protection from disinfection procedures. This review collates the literature describing interactions between and protozoan hosts in hospital and municipal potable water distribution systems. The effectiveness of currently available water disinfection protocols to control and its protozoan hosts is explored. The studies identified in this systematic literature review demonstrated the failure of common disinfection procedures to achieve long term elimination of and protozoan hosts from potable water. It has been demonstrated that protozoan hosts facilitate the intracellular replication and packaging of viable in infectious vesicles; whereas, cyst-forming protozoans provide protection from prolonged environmental stress. Disinfection procedures and protozoan hosts also facilitate biogenesis of viable but non-culturable (VBNC) which have been shown to be highly resistant to many water disinfection protocols. In conclusion, a better understanding of -protozoan interactions and the structure of complex microbial biofilms is required for the improved management of and the prevention of LD.
PubMed: 32326561
DOI: 10.3390/pathogens9040286 -
Infection and Drug Resistance 2023We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee...
We report a case of a 34-year-old lady with multiple joint pain. Autoimmune diseases were considered first with a positive result of anti-Ro antibody and her right knee joint cavity effusion. Later, bilateral interstitial changes in her lungs and mediastinal lymphadenopathy were found after chest CT scanning. Empirical quinolone therapy was given although pathological examinations of blood, sputum and bronchoalveolar lavage fluid (BALF) did not find anything. Finally, was identified by target next-generation sequencing (tNGS) detection. This case highlighted the timely use of tNGS, a new tool with fast speed, high accuracy and effective cost, could help to identify atypical infection and start an early therapy.
PubMed: 37435234
DOI: 10.2147/IDR.S417495 -
Life Science Alliance Jun 2022serogroup 1 (Lp1) sequence type (ST) 23 is one of the most commonly detected STs in Italy where it currently causes all investigated outbreaks. ST23 has caused both...
serogroup 1 (Lp1) sequence type (ST) 23 is one of the most commonly detected STs in Italy where it currently causes all investigated outbreaks. ST23 has caused both epidemic and sporadic cases between 1995 and 2018 and was analysed at genomic level and compared with ST23 isolated in other countries to determine possible similarities and differences. A core genome multi-locus sequence typing (cgMLST), based on a previously described set of 1,521 core genes, and single-nucleotide polymorphisms (SNPs) approaches were applied to an ST23 collection including genomes from Italy, France, Denmark and Scotland. DNAs were automatically extracted, libraries prepared using NextEra library kit and MiSeq sequencing performed. Overall, 63 among clinical and environmental Italian Lp1 isolates and a further seven and 11 ST23 from Denmark and Scotland, respectively, were sequenced, and pangenome analysed. Both cgMLST and SNPs analyses showed very few loci and SNP variations in ST23 genomes. All the ST23 causing outbreaks and sporadic cases in Italy and elsewhere, were phylogenetically related independent of year, town or country of isolation. Distances among the ST23s were further shortened when SNPs due to horizontal gene transfers were removed. The Lp1 ST23 isolated in Italy have kept their monophyletic origin, but they are phylogenetically close also to ST23 from other countries. The ST23 are quite widespread in Italy, and a thorough epidemiological investigation is compelled to determine sources of infection when this ST is identified in both LD sporadic cases and outbreaks.
Topics: Disease Outbreaks; Humans; Legionella pneumophila; Legionnaires' Disease; Multilocus Sequence Typing; Serogroup
PubMed: 35236759
DOI: 10.26508/lsa.202101117 -
Metabolites May 2022spp. cause Legionnaires' disease with pneumonia as the predominant clinical symptom. is the second most prevalent causative agent of community-acquired pneumonia after...
spp. cause Legionnaires' disease with pneumonia as the predominant clinical symptom. is the second most prevalent causative agent of community-acquired pneumonia after . The study aimed to characterize the lipidome of membranes and the importance of these analyses in bacterial chemotaxonomy. Lipidomic analyses based on ultra-high performance liquid chromatography-mass spectrometry allowed the detection of individual molecular species of a wide range of membrane lipids contained in the outer (OM) and inner membranes (IM). The lipid profile comprised glycerolipids (triglycerides, diglycerides), phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, cardiolipin), and sphingolipids (ceramides, hexosylceramides). The most abundant lipid fraction in the IM and OM were phospholipids. The lipidomic analysis showed that two independent phosphatidylcholine (PC) synthesis pathways operating in : the PE-methylation (PmtA) pathway and the PC synthase (Pcs) pathway. Comparison of the molecular profile of PC species contained in the lipids of membranes cultured on the medium, with and without exogenous choline, showed quantitative differences in the PC pool. An unusual feature of the lipids was the presence of ceramides and hexosylceramides, which are typical components of eukaryotic cells and a very small group of bacteria. To the best of our knowledge, this is the first report of the occurrence of ceramides in bacteria.
PubMed: 35629922
DOI: 10.3390/metabo12050418