scholarly journals Analysis of melanotic Plasmodium spp. capsules in mosquitoes reveal eumelanin-pheomelanin composition and identify AgMesh as a modulator of parasite infection

2021 ◽  
Author(s):  
Emma Camacho ◽  
Yuemei Dong ◽  
Yesseinia Anglero-Rodriguez ◽  
Daniel Smith ◽  
Ricardo S Jacomini ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Parasite Infection ◽  
Immune Defense ◽  
Insect Vector ◽  
Immune Recognition ◽  
Block Transmission ◽  
Chemical Signatures ◽  
Domains Of Life ◽  
Highly Hydrophobic ◽  
And Function

Melanins are structurally complex pigments produced by organisms in all domains of life from bacteria to animals, including humans. In insects, melanins are essential for survival and have key roles in cuticle sclerotization, wound healing and innate immunity. In this study, we used a diverse set of molecular, biochemical, and imaging approaches to characterize mosquito melanin involved in innate immune defense (melanotic capsules ). We observed that melanotic capsules enclosing Plasmodium berghei ookinetes were composed of an acid-resistant and highly hydrophobic material with granular appearance, which are characteristic properties of melanins. Spectroscopical analyses reveal chemical signatures of eumelanins and pheomelanin. Furthermore, using an enrichment approach for the proteomic analysis, we identified a set of 14 of acid-resistant mosquito proteins embedded within the melanin matrix possibly related to an anti- Plasmodium response. Among these, Ag Mesh, a highly conserved protein among insect species that contains domains suggesting a role in immune recognition and function. We targeted Ag Mesh for further study using a RNAi-based gene silencing approach in mosquitos and challenged them with two Plasmodium spp. Surprisingly, Ag Mesh gene silencing in mosquitos was associated with reduced parasite infection, implying an important role in facilitating vector infection by Plasmodium spp. Our results provide a new approach to study aspects of insect melanogenesis that revealed proteins associated with melanotic capsule, one of which was strongly implicated in the pathogenesis of Plasmodium spp. mosquito infection. Given the conservation of Ag Mesh among disease-transmitting insect vector species, future analysis of this protein could provide fertile ground for the identification of strategies that block transmission of disease to humans.

Redox-Active Selenium in Health and Disease: A Conceptual Review

2019 ◽  
Vol 19 (9) ◽  
pp. 720-726 ◽  
Author(s):  
Boguslaw Lipinski
Keyword(s):  
Food Supplement ◽  
Biologically Active ◽  
Immune Recognition ◽  
Potential Candidate ◽  
Irreversible Damage ◽  
Human Fibrinogen ◽  
Virus Attachment ◽  
Redox Active ◽  
Health And Disease ◽  
Highly Hydrophobic

Although it is generally accepted that selenium (Se) is important for life, it is not well known which forms of organic and/or inorganic Se compound are the most biologically active. In nature Se exists mostly in two forms, namely as selenite with fourvalent and selenate with sixvalent cations, from which all other inorganic and organic species are derived. Despite a small difference in their electronic structure, these two inorganic parent compounds differ significantly in their redox properties. Hence, only selenite can act as an oxidant, particularly in the reaction with free and/or protein- bound sulhydryl (SH) groups. For example, selenite was shown to inhibit the hydroxyl radicalinduced reduction and scrambled reoxidation of disulfides in human fibrinogen thus preventing the formation of highly hydrophobic polymer, termed parafibrin. Such a polymer, when deposited within peripheral and/or cerebral circulation, may cause irreversible damage resulting in the development of cardiovascular, neurological and other degenerative diseases. In addition, parafibrin deposited around tumor cells produces a protease-resistant coat protecting them against immune recognition and elimination. On the other hand, parafibrin generated by Ebola’s protein disulfide isomerase can form a hydrophobic ‘spike’ that facilitates virus attachment and entry to the host cell. In view of these specific properties of selenite this compound is a potential candidate as an inexpensive and readily available food supplement in the prevention and/or treatment of cardiovascular, neoplastic, neurological and infectious diseases.

scholarly journals Captivating Perplexities of Spinareovirinae 5′ RNA Caps

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 294
Author(s):  
Justine Kniert ◽  
Qi Feng Lin ◽  
Maya Shmulevitz
Keyword(s):  
Immune Recognition ◽  
Domains Of Life ◽  
The Many ◽  
Rna Capping ◽  
Multiple Domains ◽  
Rna Caps

RNAs with methylated cap structures are present throughout multiple domains of life. Given that cap structures play a myriad of important roles beyond translation, such as stability and immune recognition, it is not surprising that viruses have adopted RNA capping processes for their own benefit throughout co-evolution with their hosts. In fact, that RNAs are capped was first discovered in a member of the Spinareovirinae family, Cypovirus, before these findings were translated to other domains of life. This review revisits long-past knowledge and recent studies on RNA capping among members of Spinareovirinae to help elucidate the perplex processes of RNA capping and functions of RNA cap structures during Spinareovirinae infection. The review brings to light the many uncertainties that remain about the precise capping status, enzymes that facilitate specific steps of capping, and the functions of RNA caps during Spinareovirinae replication.

Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids

2018 ◽  
Vol 72 (1) ◽  
pp. 447-478 ◽  
Author(s):  
Xiaojun Tan ◽  
Lijun Sun ◽  
Jueqi Chen ◽  
Zhijian J. Chen
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Immune Defense ◽  
Innate Immune ◽  
Type I Interferons ◽  
Microbial Pathogens ◽  
Type I ◽  
Immune Recognition ◽  
Microbial Infection ◽  
Microbial Infections

Microbial infections are recognized by the innate immune system through germline-encoded pattern recognition receptors (PRRs). As most microbial pathogens contain DNA and/or RNA during their life cycle, nucleic acid sensing has evolved as an essential strategy for host innate immune defense. Pathogen-derived nucleic acids with distinct features are recognized by specific host PRRs localized in endolysosomes and the cytosol. Activation of these PRRs triggers signaling cascades that culminate in the production of type I interferons and proinflammatory cytokines, leading to induction of an antimicrobial state, activation of adaptive immunity, and eventual clearance of the infection. Here, we review recent progress in innate immune recognition of nucleic acids upon microbial infection, including pathways involving endosomal Toll-like receptors, cytosolic RNA sensors, and cytosolic DNA sensors. We also discuss the mechanisms by which infectious microbes counteract host nucleic acid sensing to evade immune surveillance.

Nonmalignant Disorders of Leukocytes

2011 ◽  
Author(s):  
Alison M. Schram ◽  
Nancy Berliner
Keyword(s):  
Blood Cells ◽  
Langerhans Cell Histiocytosis ◽  
White Blood Cells ◽  
Cell Types ◽  
Immune Defense ◽  
Cancer Surveillance ◽  
Vasoactive Substances ◽  
Clinical Disorders ◽  
Life Threatening ◽  
And Function

Leukocytes, also known as white blood cells, are hematologic cells important for a host’s immune defense. They comprise several diverse cell types including lymphocytes, neutrophils, monocytes, macrophages, and eosinophils. Each plays a unique and important role in fighting infection, cancer surveillance, and maintaining immune homeostasis. Leukocytes exert their effect and interact with host and foreign cells through the release of cytokines, chemokines, enzymes, and vasoactive substances. Altered number and function of these cells can lead to clinical disorders that range from benign to severe and life-threatening. Here we review the diagnosis, natural history, and treatment of nonmalignant disorders of leukocytes. This review contains 100 references, 6 figures, and 9 tables. Key Words: eosinophilia, hemophagocytic histiocytosis, Langerhans cell histiocytosis, lymphocytopenia, lymphocytosis mastocytosis, neutropenia, neutrophilia

scholarly journals Molybdenum Enzymes and How They Support Virulence in Pathogenic Bacteria

2020 ◽  
Vol 11 ◽  
Author(s):  
Qifeng Zhong ◽  
Bostjan Kobe ◽  
Ulrike Kappler
Keyword(s):  
Drug Targets ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogens ◽  
Energy Generation ◽  
Cellular Functions ◽  
Pathogen Fitness ◽  
Future Drug ◽  
Domains Of Life ◽  
Cofactor Biosynthesis ◽  
And Function

Mononuclear molybdoenzymes are highly versatile catalysts that occur in organisms in all domains of life, where they mediate essential cellular functions such as energy generation and detoxification reactions. Molybdoenzymes are particularly abundant in bacteria, where over 50 distinct types of enzymes have been identified to date. In bacterial pathogens, all aspects of molybdoenzyme biology such as molybdate uptake, cofactor biosynthesis, and function of the enzymes themselves, have been shown to affect fitness in the host as well as virulence. Although current studies are mostly focused on a few key pathogens such as Escherichia coli, Salmonella enterica, Campylobacter jejuni, and Mycobacterium tuberculosis, some common themes for the function and adaptation of the molybdoenzymes to pathogen environmental niches are emerging. Firstly, for many of these enzymes, their role is in supporting bacterial energy generation; and the corresponding pathogen fitness and virulence defects appear to arise from a suboptimally poised metabolic network. Secondly, all substrates converted by virulence-relevant bacterial Mo enzymes belong to classes known to be generated in the host either during inflammation or as part of the host signaling network, with some enzyme groups showing adaptation to the increased conversion of such substrates. Lastly, a specific adaptation to bacterial in-host survival is an emerging link between the regulation of molybdoenzyme expression in bacterial pathogens and the presence of immune system-generated reactive oxygen species. The prevalence of molybdoenzymes in key bacterial pathogens including ESKAPE pathogens, paired with the mounting evidence of their central roles in bacterial fitness during infection, suggest that they could be important future drug targets.

scholarly journals Structural Insight into the Mechanism of N-Linked Glycosylation by Oligosaccharyltransferase

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 624 ◽  
Author(s):  
Smita Mohanty ◽  
Bharat P Chaudhary ◽  
David Zoetewey
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Modification ◽  
Cell Communication ◽  
Reticulum Cell ◽  
Enzyme Complex ◽  
Single Polypeptide Chain ◽  
Domains Of Life ◽  
And Function ◽  
Insight Into

Asparagine-linked glycosylation, also known as N-linked glycosylation is an essential and highly conserved post-translational protein modification that occurs in all three domains of life. This modification is essential for specific molecular recognition, protein folding, sorting in the endoplasmic reticulum, cell–cell communication, and stability. Defects in N-linked glycosylation results in a class of inherited diseases known as congenital disorders of glycosylation (CDG). N-linked glycosylation occurs in the endoplasmic reticulum (ER) lumen by a membrane associated enzyme complex called the oligosaccharyltransferase (OST). In the central step of this reaction, an oligosaccharide group is transferred from a lipid-linked dolichol pyrophosphate donor to the acceptor substrate, the side chain of a specific asparagine residue of a newly synthesized protein. The prokaryotic OST enzyme consists of a single polypeptide chain, also known as single subunit OST or ssOST. In contrast, the eukaryotic OST is a complex of multiple non-identical subunits. In this review, we will discuss the biochemical and structural characterization of the prokaryotic, yeast, and mammalian OST enzymes. This review explains the most recent high-resolution structures of OST determined thus far and the mechanistic implication of N-linked glycosylation throughout all domains of life. It has been shown that the ssOST enzyme, AglB protein of the archaeon Archaeoglobus fulgidus, and the PglB protein of the bacterium Campylobactor lari are structurally and functionally similar to the catalytic Stt3 subunit of the eukaryotic OST enzyme complex. Yeast OST enzyme complex contains a single Stt3 subunit, whereas the human OST complex is formed with either STT3A or STT3B, two paralogues of Stt3. Both human OST complexes, OST-A (with STT3A) and OST-B (containing STT3B), are involved in the N-linked glycosylation of proteins in the ER. The cryo-EM structures of both human OST-A and OST-B complexes were reported recently. An acceptor peptide and a donor substrate (dolichylphosphate) were observed to be bound to the OST-B complex whereas only dolichylphosphate was bound to the OST-A complex suggesting disparate affinities of two OST complexes for the acceptor substrates. However, we still lack an understanding of the independent role of each eukaryotic OST subunit in N-linked glycosylation or in the stabilization of the enzyme complex. Discerning the role of each subunit through structure and function studies will potentially reveal the mechanistic details of N-linked glycosylation in higher organisms. Thus, getting an insight into the requirement of multiple non-identical subunits in the N-linked glycosylation process in eukaryotes poses an important future goal.

Drivers of persistent infection: pathogen-induced extracellular vesicles

2018 ◽  
Vol 62 (2) ◽  
pp. 135-147 ◽  
Author(s):  
Michael J. Cipriano ◽  
Stephen L. Hajduk
Keyword(s):  
Immune Responses ◽  
Extracellular Vesicles ◽  
Host Cells ◽  
Infected Host ◽  
Immune Recognition ◽  
Adhesive Properties ◽  
Host Immune Responses ◽  
Recognition And Response ◽  
And Function ◽  
Induced Changes

Extracellular vesicles (EVs) are produced by invading pathogens and also by host cells in response to infection. The origin, composition, and function of EVs made during infection are diverse and provide effective vehicles for localized and broad dissimilation of effector molecules in the infected host. Extracellular pathogens use EVs to communicate with each other by sensing the host environment contributing to social motility, tissue tropism, and persistence of infection. Pathogen-derived EVs can also interact with host cells to influence the adhesive properties of host membranes and to alter immune recognition and response. Intracellular pathogens can affect both the protein and RNA content of EVs produced by infected host cells. Release of pathogen-induced host EVs can affect host immune responses to infection. In this review, we will describe both the biogenesis and content of EVs produced by a number of diverse pathogens. In addition, we will examine the pathogen-induced changes to EVs produced by infected host cells.

scholarly journals Prokaryotic Argonaute from Archaeoglobus fulgidus interacts with DNA as a homodimer

2020 ◽  
Author(s):  
Edvardas Golovinas ◽  
Danielis Rutkauskas ◽  
Elena Manakova ◽  
Marija Jankunec ◽  
Arunas Silanskas ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Single Molecule ◽  
Full Length ◽  
Archaeoglobus Fulgidus ◽  
Piwi Domain ◽  
Single Molecule Fret ◽  
Dna Loop ◽  
Domains Of Life ◽  
Monomeric Proteins ◽  
And Function

ABSTRACTBackgroundArgonaute (Ago) proteins are found in all three domains of life. The best characterized group is eukaryotic Argonautes (eAgos), which are the core of RNA interference. The best understood prokaryotic Ago (pAgo) proteins are full-length pAgos. They are monomeric proteins, all composed of four major structural/functional domains (N, PAZ, MID and PIWI) and thereby closely resemble eAgos. It is believed that full-length pAgos function as prokaryotic antiviral systems, with the PIWI domain performing cleavage of invading nucleic acids. However, the majority of identified pAgos are shorter and catalytically inactive (encode just MID and inactive PIWI domains), thus their action mechanism and function remain unknown.ResultsIn this work we focus on AfAgo, a short pAgo protein encoded by an archaeon Archaeoglobus fulgidus. We find that in all previously solved AfAgo structures, its two monomers form substantial dimerization interfaces involving the C-terminal β-sheets. Led by this finding, we have employed various biochemical and biophysical assays, including single-molecule FRET, SAXS and AFM, to test the possible dimerization of AfAgo. SAXS results confirm that WT AfAgo, but not the dimerization surface mutant AfAgoΔ, forms a homodimer both in the apo-form and when bound to a nucleic acid. Single molecule FRET and AFM studies demonstrate that the dimeric WT AfAgo binds two ends of a linear DNA fragment, forming a relatively stable DNA loop.ConclusionOur results show that contrary to other characterized Ago proteins, AfAgo is a stable homodimer in solution, which is capable of simultaneous interaction with two DNA molecules. This finding broadens the range of currently known Argonaute-nucleic acid interaction mechanisms.

scholarly journals Optimization of Methods for the Accurate Characterization of Whole Blood Neutrophils

2021 ◽  
Author(s):  
Ashley N. Connelly ◽  
Richard P.H. Huijbregts ◽  
Harish C. Pal ◽  
Valeriya Kuznetsova ◽  
Marcus D. Davis ◽  
...  
Keyword(s):  
Whole Blood ◽  
Neutrophil Activation ◽  
Immune Defense ◽  
Experimental Conditions ◽  
Adaptive Immune ◽  
Blood Neutrophils ◽  
One Step ◽  
And Function ◽  
Adaptive Immune Systems

Abstract Neutrophils are the most abundant circulating leukocyte population with critical roles in immune defense, regulation of innate and adaptive immune systems, and disease pathogenesis. Our progress in understanding precise mechanisms of neutrophil activation, recruitment, and function has been hampered by the lack of optimized and standardized methods for the characterization and phenotyping of this readily activated population. By comparing eight methods of neutrophil characterization, we demonstrate that the level of neutrophil activation and degranulation is associated with specific experimental conditions and the number and type of manipulation steps employed. Staining whole blood at 4ºC and removal of remaining unbound antibodies prior to one-step fixation and red blood cell lysis minimizes neutrophil activation, decreases phenotypic alterations during processing, and prevents nonspecific antibody binding. The effects of anticoagulants used for collection, processing delays, and time and temperature during sample analysis on neutrophil phenotype are addressed. The presented data provide a foundation for higher quality standards of neutrophil characterization improving consistency and reproducibility among studies.

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