Glycocalyx crowding with mucin mimetics strengthens binding of soluble and virus-associated lectins to host cell glycan receptors

2021 ◽  
Vol 118 (40) ◽  
pp. e2107896118
Author(s):  
Daniel J. Honigfort ◽  
Meghan O. Altman ◽  
Pascal Gagneux ◽  
Kamil Godula

Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving as nonproductive decoys that capture infectious agents and clear them from the cell surface and by erecting a physical barrier that restricts their access to target receptors on host cells. However, the mechanisms through which mucins function are still poorly defined because of a limited repertoire of tools available for tailoring their structure and composition in living cells with molecular precision. Using synthetic glycopolymer mimetics of mucins, we modeled the mucosal glycocalyx on red blood cells (RBCs) and evaluated its influence on lectin (SNA) and virus (H1N1) adhesion to endogenous sialic acid receptors. The glycocalyx inhibited the rate of SNA and H1N1 adhesion in a size- and density-dependent manner, consistent with the current view of mucins as providing a protective shield against pathogens. Counterintuitively, increasing the density of the mucin mimetics enhanced the retention of bound lectins and viruses. Careful characterization of SNA behavior at the RBC surface using a range of biophysical and imaging techniques revealed lectin-induced crowding and reorganization of the glycocalyx with concomitant enhancement in lectin clustering, presumably through the formation of a more extensive glycan receptor patch at the cell membrane. Our findings indicate that glycan-targeting pathogens may exploit the biophysical and biomechanical properties of mucins to overcome the mucosal glycocalyx barrier.

2021 ◽  
Author(s):  
Daniel J Honigfort ◽  
Meghan O'Donoghue Altman ◽  
Pascal Gagneux ◽  
Kamil Godula

Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving as non-productive decoys that capture infectious agents and clear them from the cell surface and by erecting a physical barrier that restricts their access to target receptors on host cells. However, the mechanisms through which mucins function are still poorly defined due to a limited repertoire of tools available for tailoring their structure and composition in living cells with molecular precision. Using synthetic glycopolymer mimetics of mucins, we modeled the mucosal glycocalyx on red blood cells (RBC) and evaluated its influence on lectin (SNA) and virus (H1N1) adhesion to endogenous sialic acid receptors. The glycocalyx inhibited the rate of SNA and H1N1 adhesion in a size- and density-dependent manner, consistent with current view of the mucins as providing a protective shield against pathogens. Counterintuitively, increasing density of the mucin mimetics enhanced the retention of bound lectins and viruses. Careful characterization of SNA behavior at the RBC surface using a range of biophysical and imaging techniques revealed lectin-induced crowding and reorganization of the glycocalyx with concomitant enhancement in lectin clustering, presumably through the formation of a more extensive glycan receptor patch at the cell surface. Our findings indicate that glycan-targeting pathogens may exploit the biophysical and biomechanical properties of mucins to overcome the mucosal glycocalyx barrier.


2014 ◽  
Vol 11 (2) ◽  
pp. 17-23
Author(s):  
Myagmarsuren Punsantsogvoo ◽  
Hany Ibrahim ◽  
Narantsatsral Sandagdorj ◽  
Battur Banzragch ◽  
Battsetseg Badgar ◽  
...  

Neosporosis is caused by an intracellular protozoan,Neospora caninum, which is an important pathogen of dogs and cattle. In this study, we analyzed Neospora caninum cyclophilin 18 protein (NcCyp18), which regulates proliferation and migration of murine macrophages and lymphocytes. From our study, NcCyp18 showed the activity of macrophage proliferation in a CCR5-independent manner and activity of spleen cell proliferation in a CCR5-dependent manner. NcCyp18 showed the activity of macrophage migration in a CCR5-independent manner and activity of spleen cell migration in a CCR5-dependent manner. Moreover, recombinant NcCyp18 induced the production of the nitric oxide and IL-12 p40. The data suggest that NcCyp18 recruits host cells and enhances the growth of host cells at the site of infection for maintenance of interaction between the parasite and host. DOI: http://dx.doi.org/10.5564/mjas.v11i2.209 Mongolian Journal of Agricultural Sciences Vol.11(2) 2013 pp.17-23


2020 ◽  
Vol 17 (1) ◽  
pp. 3-9
Author(s):  
Rajdeep Das ◽  
Nisha D`souza ◽  
Surya K. Choubey ◽  
Sethumadhavan Murlidharan ◽  
Anura V. Kurpad ◽  
...  

Background: Staphylococcus aureus (S. aureus), an important pathogen, causes a wide range of infections in human starting from food poisoning to septicemia. It affects the host cells with various exotoxins, known as virulence factors, which are synthesized in growth phase-dependent manner of the bacteria. S. aureus has been reported to become resistant to antibiotics rapidly. Among two common clinical isolates, Methicillin-sensitive S. aureus (MSSA) and Methicillin-resistant S. aureus (MRSA), MRSA pose major problems across hospitals around the world. Objective: The objective of the present study was to profile the exoproteins of Methicillin-sensitive S. aureus (ATCC 25293) and subsequently to establish a proteomics-based method of characterization of S. aureus that is crucial in treating hospital-acquired infections. Methods: We used two-dimensional nanoLC/ESI-MS based proteomic platform to characterize and quantify the exoproteins isolated from Methicillin-sensitive S. aureus (ATCC 25293) strain. Results: A total of 69 proteins were identified from extracellular proteome pool of ATCC 25293 strain that includes 18 extracellular proteins, 40 cytoplasmic proteins, 2 membrane proteins, 3 cell wall proteins and 6 uncharacterized proteins. Conclusion: We propose that this mass spectrometry-based proteomics method of characterization of exoproteins might be useful to identify S. aureus strains that are resistant to antibiotics.


Author(s):  
P.A. Crozier ◽  
M. Pan

Heterogeneous catalysts can be of varying complexity ranging from single or double phase systems to complicated mixtures of metals and oxides with additives to help promote chemical reactions, extend the life of the catalysts, prevent poisoning etc. Although catalysis occurs on the surface of most systems, detailed descriptions of the microstructure and chemistry of catalysts can be helpful for developing an understanding of the mechanism by which a catalyst facilitates a reaction. Recent years have seen continued development and improvement of various TEM, STEM and AEM techniques for yielding information on the structure and chemistry of catalysts on the nanometer scale. Here we review some quantitative approaches to catalyst characterization that have resulted from new developments in instrumentation.HREM has been used to examine structural features of catalysts often by employing profile imaging techniques to study atomic details on the surface. Digital recording techniques employing slow-scan CCD cameras have facilitated the use of low-dose imaging in zeolite structure analysis and electron crystallography. Fig. la shows a low-dose image from SSZ-33 zeolite revealing the presence of a stacking fault.


Author(s):  
J. Liu ◽  
M. Pan ◽  
G. E. Spinnler

Small metal particles have peculiar chemical and physical properties as compared to bulk materials. They are especially important in catalysis since metal particles are common constituents of supported catalysts. The structural characterization of small particles is of primary importance for the understanding of structure-catalytic activity relationships. The shape and size of metal particles larger than approximately 5 nm in diameter can be determined by several imaging techniques. It is difficult, however, to deduce the shape of smaller metal particles. Coherent electron nanodiffraction (CEND) patterns from nano particles contain information about the particle size, shape, structure and defects etc. As part of an on-going program of STEM characterization of supported catalysts we report some preliminary results of CEND study of Ag nano particles, deposited in situ in a UHV STEM instrument, and compare the experimental results with full dynamical simulations in order to extract information about the shape of Ag nano particles.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3645
Author(s):  
Isabel Theresa Schobert ◽  
Lynn Jeanette Savic

With the increasing understanding of resistance mechanisms mediated by the metabolic reprogramming in cancer cells, there is a growing clinical interest in imaging technologies that allow for the non-invasive characterization of tumor metabolism and the interactions of cancer cells with the tumor microenvironment (TME) mediated through tumor metabolism. Specifically, tumor glycolysis and subsequent tissue acidosis in the realms of the Warburg effect may promote an immunosuppressive TME, causing a substantial barrier to the clinical efficacy of numerous immuno-oncologic treatments. Thus, imaging the varying individual compositions of the TME may provide a more accurate characterization of the individual tumor. This approach can help to identify the most suitable therapy for each individual patient and design new targeted treatment strategies that disable resistance mechanisms in liver cancer. This review article focuses on non-invasive positron-emission tomography (PET)- and MR-based imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism.


2021 ◽  
Vol 22 (14) ◽  
pp. 7669
Author(s):  
Cassio Luiz Coutinho Almeida-da-Silva ◽  
Harmony Matshik Dakafay ◽  
Kaitlyn Liu ◽  
David M. Ojcius

A large body of evidence shows the harmful effects of cigarette smoke to oral and systemic health. More recently, a link between smoking and susceptibility to coronavirus disease 2019 (COVID-19) was proposed. COVID-19 is due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses the receptor ACE2 and the protease TMPRSS2 for entry into host cells, thereby infecting cells of the respiratory tract and the oral cavity. Here, we examined the effects of cigarette smoke on the expression of SARS-CoV-2 receptors and infection in human gingival epithelial cells (GECs). We found that cigarette smoke condensates (CSC) upregulated ACE2 and TMPRSS2 expression in GECs, and that CSC activated aryl hydrocarbon receptor (AhR) signaling in the oral cells. ACE2 was known to mediate SARS-CoV-2 internalization, and we demonstrate that CSC treatment potentiated the internalization of SARS-CoV-2 pseudovirus in GECs in an AhR-dependent manner. AhR depletion using small interference RNA decreased SARS-CoV-2 pseudovirus internalization in CSC-treated GECs compared with control GECs. Our study reveals that cigarette smoke upregulates SARS-CoV-2 receptor expression and infection in oral cells. Understanding the mechanisms involved in SARS-CoV-2 infection in cells of the oral cavity may suggest therapeutic interventions for preventing viral infection and transmission.


2021 ◽  
Vol 9 (1) ◽  
pp. 7
Author(s):  
Geoffrey W. Peitz ◽  
Elisabeth A. Wilde ◽  
Ramesh Grandhi

Magnetoencephalography (MEG) is a functional brain imaging technique with high temporal resolution compared with techniques that rely on metabolic coupling. MEG has an important role in traumatic brain injury (TBI) research, especially in mild TBI, which may not have detectable features in conventional, anatomical imaging techniques. This review addresses the original research articles to date that have reported on the use of MEG in TBI. Specifically, the included studies have demonstrated the utility of MEG in the detection of TBI, characterization of brain connectivity abnormalities associated with TBI, correlation of brain signals with post-concussive symptoms, differentiation of TBI from post-traumatic stress disorder, and monitoring the response to TBI treatments. Although presently the utility of MEG is mostly limited to research in TBI, a clinical role for MEG in TBI may become evident with further investigation.


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