scholarly journals Differential Requirements for Mediator Complex Subunits in Drosophila melanogaster Host Defense Against Fungal and Bacterial Pathogens

2021 ◽  
Vol 11 ◽  
Author(s):  
Chuqin Huang ◽  
Rui Xu ◽  
Samuel Liégeois ◽  
Di Chen ◽  
Zi Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Host Defense ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Transcriptional Response ◽  
Erwinia Carotovora ◽  
Mediator Complex ◽  
Toll Pathway ◽  
Metarhizium Robertsii ◽  
Immune Factor

The humoral immune response to bacterial or fungal infections in Drosophila relies largely on a transcriptional response mediated by the Toll and Immune deficiency NF-κB pathways. Antimicrobial peptides are potent effectors of these pathways and allow the organism to attack invading pathogens. Dorsal-related Immune Factor (DIF), a transcription factor regulated by the Toll pathway, is required in the host defense against fungal and some Gram-positive bacterial infections. The Mediator complex is involved in the initiation of transcription of most RNA polymerase B (PolB)-dependent genes by forming a functional bridge between transcription factors bound to enhancer regions and the gene promoter region and then recruiting the PolB pre-initiation complex. Mediator is formed by several modules that each comprises several subunits. The Med17 subunit of the head module of Mediator has been shown to be required for the expression of Drosomycin, which encodes a potent antifungal peptide, by binding to DIF. Thus, Mediator is expected to mediate the host defense against pathogens controlled by the Toll pathway-dependent innate immune response. Here, we first focus on the Med31 subunit of the middle module of Mediator and find that it is required in host defense against Aspergillus fumigatus, Enterococcus faecalis, and injected but not topically-applied Metarhizium robertsii. Thus, host defense against M. robertsii requires Dif but not necessarily Med31 in the two distinct infection models. The induction of some Toll-pathway-dependent genes is decreased after a challenge of Med31 RNAi-silenced flies with either A. fumigatus or E. faecalis, while these flies exhibit normal phagocytosis and melanization. We have further tested most Mediator subunits using RNAi by monitoring their survival after challenges to several other microbial infections known to be fought off through DIF. We report that the host defense against specific pathogens involves a distinct set of Mediator subunits with only one subunit for C. glabrata or Erwinia carotovora carotovora, at least one for M. robertsii or a somewhat extended repertoire for A. fumigatus (at least eight subunits) and E. faecalis (eight subunits), with two subunits, Med6 and Med11 being required only against A. fumigatus. Med31 but not Med17 is required in fighting off injected M. robertsii conidia. Thus, the involvement of Mediator in Drosophila innate immunity is more complex than expected.

scholarly journals The BaramicinA gene is required at several steps of the host defense against Enterococcus faecalis and Metarhizium robertsii in a septic wound infection model in Drosophila melanogaster

2020 ◽  
Author(s):  
Jianqiong Huang ◽  
Yanyan Lou ◽  
Jiyong Liu ◽  
Philippe Bulet ◽  
Renjie Jiao ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Host Defense ◽  
Fungal Infections ◽  
Sequence Similarity ◽  
Infection Model ◽  
Toll Pathway ◽  
Phenotypic Analysis ◽  
Gram Positive ◽  
Furin Cleavage ◽  
Metarhizium Robertsii

AbstractThe host defense against several Gram-positive bacterial and fungal infections is mostly mediated by the Toll pathway in Drosophila, which regulates the expression of multiple genes including effectors of the innate immune response. One such potential effector is IMPPP/BaraA, a precursor protein that is processed at furin cleavage sites into an armamentarium of small DIM peptides that display a high degree of sequence similarity. We report here the generation of multiple mutants affecting this gene. Our phenotypic analysis revealed a specific sensitivity to pathogens belonging to distinct kingdoms, the Gram-positive bacterium Enterococcus faecalis and the entomopathogenic fungus Metarhizium anisopliae, only in septic injury models of infection. Unexpectedly, we failed to reveal a consistently increased microbial burden in the mutant flies infected with either of these microorganisms, opening the possibility for a role of BaraA in resilience rather than in resistance, which we were however unable to confirm. We also found that some BaraA-derived DIM peptides display an antimicrobial activity at millimolar concentrations in vitro. BaraA is additionally required for an efficient cleavage of pro-phenol oxidase into an active enzyme. BaraA is also involved in the cellular host defense, but through distinct mechanisms: it needs to be expressed in hemocytes for an efficient response solely to E. faecalis infection whereas it is required for the uptake by plasmatocytes of M. robertsii conidia. We propose a model whereby BaraA secreted by hemocytes may act at a very short range and protect host tissues or organs targeted specifically by E. faecalis. This study thus reveals an unexpected functional complexity of a potential effector of the Toll pathway in the host defense against specific infections.

scholarly journals Identification of the Ricin-B-Lectin LdRBLk in the Colorado Potato Beetle and an Analysis of Its Expression in Response to Fungal Infections

2021 ◽  
Vol 7 (5) ◽  
pp. 364
Author(s):  
Ulyana Rotskaya ◽  
Vadim Kryukov ◽  
Elena Kosman ◽  
Maksim Tyurin ◽  
Viktor Glupov
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Colorado Potato Beetle ◽  
Leptinotarsa Decemlineata ◽  
Fat Body ◽  
Fungal Infections ◽  
Ricinus Communis ◽  
Metarhizium Robertsii ◽  
Expression Levels ◽  
Potato Beetle

Ricin-B-lectins (RBLs) have been identified in many groups of organisms, including coleopterans insects, particularly the Colorado potato beetle Leptinotarsa decemlineata (LdRBLs). We hypothesized that one of these LdRBLs (LdRBLk) may be involved in the immune response to fungal infections. We performed a theoretical analysis of the structure of this protein. Additionally, the expression levels of the LdRBlk gene were measured in L. decemlineata in response to infections with the fungi Metarhizium robertsii and Beauveria bassiana. The expression levels of LdRBlk in the L. decemlineata cuticle and fat body were increased in response to both infections. The induction of LdRBlk expression was dependent on the susceptibility of larvae to the fungi. Upregulation of the LdRBlk gene was also observed in response to other stresses, particularly thermal burns. Elevation of LdRBlk expression was frequently observed to be correlated with the expression of the antimicrobial peptide attacin but was not correlated with hsp90 regulation. Commercially available β-lectin of ricin from Ricinus communis was observed to inhibit the germination of conidia of the fungi. We suggest that LdRBLk is involved in antifungal immune responses in the Colorado potato beetle, either exerting fungicidal properties directly or acting as a modulator of the immune response.

Application of Innovative Hydroxyapatite Materials in 3D Printing for Biocompatible Voice Implants

2018 ◽  
Vol 69 (4) ◽  
pp. 840-842
Author(s):  
Wojciech Musialik ◽  
Marcin Nabialek ◽  
Slawomir Letkiewicz ◽  
Andrei Victor Sandu ◽  
Katarzyna Bloch
Keyword(s):  
3D Printing ◽  
Surgical Procedures ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Colloidal Silver ◽  
Bone Implants ◽  
External Ring ◽  
Voice Prostheses ◽  
3D Printers ◽  
Silver Composite

The paper presents the possibility of using an innovative hydroxyapatite filament Ca10(PO4)6(OH)2 for printing in 3D printers of bone implants and the possibility of using it during implantation with voice prostheses. The introduction of an additional colloidal silver composite in voice implants will contribute to the reduction of bacterial infections, fungal infections and granulomatous hyperplasia. The creation of a stable external ring of the vocal fistula will remove complications associated with it with enlargement of the fistula and leakiness of voice implants. The ability to print with a hydroxyapatite filament will allow digital pre-surgery modeling of bone implants suited to the needs of surgical procedures.

Heterocycle Compounds with Antimicrobial Activity

2020 ◽  
Vol 26 (8) ◽  
pp. 867-904 ◽  
Author(s):  
Maria Fesatidou ◽  
Anthi Petrou ◽  
Geronikaki Athina
Keyword(s):  
Heterocyclic Compounds ◽  
Bacterial Infections ◽  
Scientific Community ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Biological Activities ◽  
Literature Survey ◽  
New Findings ◽  
Wide Range ◽  
Number Of Microorganisms

Background: Bacterial infections are a growing problem worldwide causing morbidity and mortality mainly in developing countries. Moreover, the increased number of microorganisms, developing multiple resistances to known drugs, due to abuse of antibiotics, is another serious problem. This problem becomes more serious for immunocompromised patients and those who are often disposed to opportunistic fungal infections. Objective: The objective of this manuscript is to give an overview of new findings in the field of antimicrobial agents among five-membered heterocyclic compounds. These heterocyclic compounds especially five-membered attracted the interest of the scientific community not only for their occurrence in nature but also due to their wide range of biological activities. Method: To reach our goal, a literature survey that covers the last decade was performed. Results: As a result, recent data on the biological activity of thiazole, thiazolidinone, benzothiazole and thiadiazole derivatives are mentioned. Conclusion: It should be mentioned that despite the progress in the development of new antimicrobial agents, there is still room for new findings. Thus, research still continues.

scholarly journals Community-acquired and hospital-acquired respiratory tract infection and bloodstream infection in patients hospitalized with COVID-19 pneumonia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Kirstine K. Søgaard ◽  
Veronika Baettig ◽  
Michael Osthoff ◽  
Stephan Marsch ◽  
Karoline Leuzinger ◽  
...  
Keyword(s):  
Intensive Care ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Bloodstream Infection ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Icu Patients ◽  
Hospital Acquired Infections ◽  
Hospital Acquired

Abstract Objectives SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. Methods We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for < 24 h (n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections. Results In the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4–74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8–18) and time to bloodstream infection 14 days (IQR, 6–30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients. Conclusions Community-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.

scholarly journals PGC-1α mediates a metabolic host defense response in human airway epithelium during rhinovirus infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aubrey N. Michi ◽  
Bryan G. Yipp ◽  
Antoine Dufour ◽  
Fernando Lopes ◽  
David Proud
Keyword(s):  
Host Defense ◽  
Barrier Function ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
Cellular Damage ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Barrier Function ◽  
Epithelial Damage

AbstractHuman rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway epithelial damage and dysfunction remain undefined. Using experimental HRV infection studies in highly differentiated human bronchial epithelial cells grown at air-liquid interface (ALI), we examine the links between viral host defense, cellular metabolism, and epithelial barrier function. We observe that early HRV-C15 infection induces a transitory barrier-protective metabolic state characterized by glycolysis that ultimately becomes exhausted as the infection progresses and leads to cellular damage. Pharmacological promotion of glycolysis induces ROS-dependent upregulation of the mitochondrial metabolic regulator, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), thereby restoring epithelial barrier function, improving viral defense, and attenuating disease pathology. Therefore, PGC-1α regulates a metabolic pathway essential to host defense that can be therapeutically targeted to rescue airway epithelial barrier dysfunction and potentially prevent severe respiratory complications or secondary bacterial infections.

scholarly journals Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art

2021 ◽  
Vol 7 (6) ◽  
pp. 451
Author(s):  
Georgios Karavalakis ◽  
Evangelia Yannaki ◽  
Anastasia Papadopoulou
Keyword(s):  
Host Defense ◽  
Hematopoietic Cell Transplantation ◽  
State Of The Art ◽  
Fungal Infections ◽  
Solid Organ Transplantation ◽  
Immunocompromised Host ◽  
Antifungal Drugs ◽  
Solid Organ ◽  
Cell Immunotherapy ◽  
Life Threatening

Despite the availability of a variety of antifungal drugs, opportunistic fungal infections still remain life-threatening for immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplantation or solid organ transplantation. Suboptimal efficacy, toxicity, development of resistant variants and recurrent episodes are limitations associated with current antifungal drug therapy. Adjunctive immunotherapies reinforcing the host defense against fungi and aiding in clearance of opportunistic pathogens are continuously gaining ground in this battle. Here, we review alternative approaches for the management of fungal infections going beyond the state of the art and placing an emphasis on fungus-specific T cell immunotherapy. Harnessing the power of T cells in the form of adoptive immunotherapy represents the strenuous protagonist of the current immunotherapeutic approaches towards combating invasive fungal infections. The progress that has been made over the last years in this field and remaining challenges as well, will be discussed.

Not just vegetations: focal myocardial changes in patients with fungal infections

2020 ◽  
pp. 1-6
Author(s):  
Nicole M. Cresalia ◽  
Sonal T. Owens ◽  
Terri L. Stillwell ◽  
Mark D. Norris ◽  
Sunkyung Yu ◽  
...  
Keyword(s):  
Length Of Stay ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Positive Culture ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Similar Proportion ◽  
Retrospective Case ◽  
Fungal Endocarditis ◽  
Catheter Tip

Abstract Background: Fungal endocarditis classically involves dense heterogenous vegetations. However, several patients with fungal infections were noted to have myocardial changes ranging from focal brightening to nodular thickening of chordae or papillary muscles. This study evaluates whether these findings are associated with fungal infections. Methods: In a retrospective case–control study, paediatric inpatients with fungal infections (positive blood, urine, or catheter tip culture) in a 5-year period were matched 1:1 to inpatients without positive fungal cultures. Echocardiograms were scored on a 5-point scale by two independent readers for presence of myocardial brightenings, nodular thickenings, and vegetations. Clinical data were compared. Results: Of 67 fungal cases, positive culture sites included blood (n = 44), vascular catheter tip (n = 7), and urine (n = 29); several had multiple positive sites. “Positive” echo findings (score ≥ 2+) were more frequent in the Fungal Group (33 versus 18%, p = 0.04). Fungal Group patients with “positive” versus “negative” echo findings had similar proportion of bacterial infections. Among fungal cases, those with “positive” echo findings had longer hospital length of stay than cases with “negative” echos (median 58 versus 40 days, p = 0.03) but no difference in intensive care unit admission, extracorporeal membranous oxygenation support, or mortality. Conclusions: Myocardial and papillary muscle brightening with nodular thickening on echocardiogram appear to be associated with fungal infections. There may be prognostic implications of these findings as patients with “positive” echo have longer length of stay. Further studies are needed to better understand the mechanism and temporal progression of these changes and determine the prognostic value of this scoring system.

Topics in Chronic Granulomatous Disease

PEDIATRICS ◽  
1991 ◽  
Vol 88 (1) ◽  
pp. 183-185
Author(s):  
SHIGENOBU UMEKI
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Host Defense ◽  
Superoxide Anion ◽  
Fungal Infections ◽  
Regulatory Elements ◽  
Granulomatous Disease ◽  
Phagocytic Cells ◽  
Oxidase System ◽  
Membrane Bound

To the Editor.— Such phagocytic cells as neutrophils and macrophages are crucial elements in the host defense against bacterial [See table in the PDF file] and fungal infections. Microbicidal activity depends to a large extent on NADPH oxidase system, which can be activated by stimuli (bacteria, fungi) and which generates the superoxide anion and other highly reactive forms of reduced oxygen.1,2 The neutrophil NADPH oxidase system is composed functionally of membrane-bound catalytic components (which consist of at least two constituents, the low potential cytochrome b5583-5 and flavoprotein5) and soluble cytosolic components6,7 which participate as either catalytic or regulatory elements.

C-Reactive Protein as A Fungal Infection Marker in Acute Leukemia Patients

2021 ◽  
Vol 27 (2) ◽  
pp. 212
Author(s):  
Brigitte Rina Aninda Sidharta ◽  
JB. Suparyatmo ◽  
Avanti Fitri Astuti
Keyword(s):  
Acute Leukemia ◽  
Predictive Value ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Negative Likelihood Ratio ◽  
Receiver Operating Curve ◽  
High Morbidity ◽  
C Reactive Protein ◽  
Reactive Protein

Invasive Fungal Infections (IFIs) can cause serious problems in cancer patients and may result in high morbidity andmortality. C-reactive protein levels increase in response to injury, infection, and inflammation. C-reactive protein increasesin bacterial infections (mean of 32 mg/L) and in fungal infections (mean of 9 mg/L). This study aimed to determineC-Reactive Protein (CRP) as a marker of fungal infections in patients with acute leukemia by establishing cut-off values ofCRP. This study was an observational analytical study with a cross-sectional approach and was carried out at the Departmentof Clinical Pathology and Microbiology of Dr. Moewardi Hospital in Surakarta from May until August 2019. The inclusioncriteria were patients with acute leukemia who were willing to participate in this study, while exclusion criteria were patientswith liver disease. There were 61 samples consisting of 30 male and 31 female patients with ages ranging from 1 to 70 years.Fifty-four patients (88.5%) were diagnosed with Acute Lymphoblastic Leukemia (ALL) and 30 (49.18%) were in themaintenance phase. The risk factors found in those patients were neutropenia 50-1500 μL (23.8%), use of intravenous line(22%), and corticosteroid therapy for more than one week (20.9%). The median of CRP in the group of patients with positiveculture results was 11.20 mg/L (11.20-26.23 mg/L) and negative culture results in 0.38 mg/L (0.01-18.63 mg/L). The cut-offvalue of CRP using the Receiver Operating Curve (ROC) was 9.54 mg/L (area under curve 0.996 and p. 0.026), with a sensitivityof 100%, specificity of 93.2%, Positive Predictive Value (PPV) of 33.3%, Negative Predictive Value (PPV) of 100%, PositiveLikelihood Ratio (PLR) of 1.08, Negative Likelihood Ratio (NLR) of 0 and accuracy of 93.4%. C-reactive protein can be used asa screening marker for fungal infections in patients with acute leukemia.

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