scholarly journals Lactate cross-talk in host–pathogen interactions

2021 ◽  
Vol 478 (17) ◽  
pp. 3157-3178
Author(s):  
Alba Llibre ◽  
Frances S. Grudzinska ◽  
Matthew K. O'Shea ◽  
Darragh Duffy ◽  
David R. Thickett ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Host Cells ◽  
Host Pathogen Interactions ◽  
Signalling Molecule ◽  
Host Pathogen ◽  
Microbe Interactions ◽  
Sense And Respond ◽  
Host Microbe Interactions ◽  
Ubiquitous Presence ◽  
The Warburg Effect

Lactate is the main product generated at the end of anaerobic glycolysis or during the Warburg effect and its role as an active signalling molecule is increasingly recognised. Lactate can be released and used by host cells, by pathogens and commensal organisms, thus being essential for the homeostasis of host–microbe interactions. Infection can alter this intricate balance, and the presence of lactate transporters in most human cells including immune cells, as well as in a variety of pathogens (including bacteria, fungi and complex parasites) demonstrates the importance of this metabolite in regulating host–pathogen interactions. This review will cover lactate secretion and sensing in humans and microbes, and will discuss the existing evidence supporting a role for lactate in pathogen growth and persistence, together with lactate's ability to impact the orchestration of effective immune responses. The ubiquitous presence of lactate in the context of infection and the ability of both host cells and pathogens to sense and respond to it, makes manipulation of lactate a potential novel therapeutic strategy. Here, we will discuss the preliminary research that has been carried out in the context of cancer, autoimmunity and inflammation.

scholarly journals AFM-Based Correlative Microscopy Illuminates Human Pathogens

2021 ◽  
Vol 11 ◽  
Author(s):  
Supriya V. Bhat ◽  
Jared D. W. Price ◽  
Tanya E. S. Dahms
Keyword(s):  
Optical Microscopy ◽  
Disease Transmission ◽  
Fitness Landscape ◽  
Host Cells ◽  
Full Potential ◽  
Correlative Microscopy ◽  
Human Pathogens ◽  
Host Pathogen Interactions ◽  
Host Pathogen ◽  
The Many

Microbes have an arsenal of virulence factors that contribute to their pathogenicity. A number of challenges remain to fully understand disease transmission, fitness landscape, antimicrobial resistance and host heterogeneity. A variety of tools have been used to address diverse aspects of pathogenicity, from molecular host-pathogen interactions to the mechanisms of disease acquisition and transmission. Current gaps in our knowledge include a more direct understanding of host-pathogen interactions, including signaling at interfaces, and direct phenotypic confirmation of pathogenicity. Correlative microscopy has been gaining traction to address the many challenges currently faced in biomedicine, in particular the combination of optical and atomic force microscopy (AFM). AFM, generates high-resolution surface topographical images, and quantifies mechanical properties at the pN scale under physiologically relevant conditions. When combined with optical microscopy, AFM probes pathogen surfaces and their physical and molecular interaction with host cells, while the various modes of optical microscopy view internal cellular responses of the pathogen and host. Here we review the most recent advances in our understanding of pathogens, recent applications of AFM to the field, how correlative AFM-optical microspectroscopy and microscopy have been used to illuminate pathogenicity and how these methods can reach their full potential for studying host-pathogen interactions.

scholarly journals Spatial metabolomics of in situ, host-microbe interactions

2019 ◽  
Author(s):  
Benedikt K Geier ◽  
Emilia Sogin ◽  
Dolma Michellod ◽  
Moritz Janda ◽  
Mario Kompauer ◽  
...  
Keyword(s):  
Microbial Interactions ◽  
Host Cells ◽  
Metabolic Phenotype ◽  
Community Members ◽  
Metabolic Phenotypes ◽  
Culture Independent ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Atmospheric Pressure Mass Spectrometry

Spatial metabolomics describes the location and chemistry of small molecules involved in metabolic phenotypes, defense molecules and chemical interactions in natural communities. Most current techniques are unable to spatially link the genotype and metabolic phenotype of microorganisms in situ at a scale relevant to microbial interactions. Here, we present a spatial metabolomics pipeline (metaFISH) that combines fluorescence in situ hybridization (FISH) microscopy and high-resolution atmospheric pressure mass spectrometry imaging (AP-MALDI-MSI) to image host-microbe symbioses and their metabolic interactions. metaFISH aligns and integrates metabolite and fluorescent images at the micrometer-scale for a spatial assignment of host and symbiont metabolites on the same tissue section. To illustrate the advantages of metaFISH, we mapped the spatial metabolome of a deep-sea mussel and its intracellular symbiotic bacteria at the scale of individual epithelial host cells. Our analytical pipeline revealed metabolic adaptations of the epithelial cells to the intracellular symbionts, a variation in metabolic phenotypes in one symbiont type, and novel symbiosis metabolites. metaFISH provides a culture-independent approach to link metabolic phenotypes to community members in situ - a powerful tool for microbiologists across fields.

scholarly journals Frontline defenders: goblet cell mediators dictate host-microbe interactions in the intestinal tract during health and disease

2018 ◽  
Vol 314 (3) ◽  
pp. G360-G377 ◽  
Author(s):  
Joannie M. Allaire ◽  
Vijay Morampudi ◽  
Shauna M. Crowley ◽  
Martin Stahl ◽  
Hongbing Yu ◽  
...  
Keyword(s):  
Host Defense ◽  
Current Evidence ◽  
Gi Tract ◽  
Intestinal Mucus ◽  
Mucin 2 ◽  
Microbe Interactions ◽  
Noxious Stimuli ◽  
Sense And Respond ◽  
Mucus Barrier ◽  
Host Microbe Interactions

Goblet cells (GCs) are the predominant secretory epithelial cells lining the luminal surface of the mammalian gastrointestinal (GI) tract. Best known for their apical release of mucin 2 (Muc2), which is critical for the formation of the intestinal mucus barrier, GCs have often been overlooked for their active contributions to intestinal protection and host defense. In part, this oversight reflects the limited tools available to study their function but also because GCs have long been viewed as relatively passive players in promoting intestinal homeostasis and host defense. In light of recent studies, this perspective has shifted, as current evidence suggests that Muc2 as well as other GC mediators are actively released into the lumen to defend the host when the GI tract is challenged by noxious stimuli. The ability of GCs to sense and respond to danger signals, such as bacterial pathogens, has recently been linked to inflammasome signaling, potentially intrinsic to the GCs themselves. Moreover, further work suggests that GCs release Muc2, as well as other mediators, to modulate the composition of the gut microbiome, leading to both the expansion as well as the depletion of specific gut microbes. This review will focus on the mechanisms by which GCs actively defend the host from noxious stimuli, as well as describe advanced technologies and new approaches by which their responses can be addressed. Taken together, we will highlight current insights into this understudied, yet critical, aspect of intestinal mucosal protection and its role in promoting gut defense and homeostasis.

scholarly journals Perspectives on Remorin Proteins, Membrane Rafts, and Their Role During Plant–Microbe Interactions

2011 ◽  
Vol 24 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Iris K. Jarsch ◽  
Thomas Ott
Keyword(s):  
Current Knowledge ◽  
Root Nodules ◽  
Current Data ◽  
Effector Proteins ◽  
Host Cells ◽  
Membrane Microdomains ◽  
Membrane Rafts ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Molecular Patterns

Invasion of host cells by pathogenic or mutualistic microbes requires complex molecular dialogues that often determine host survival. Although several components of the underlying signaling cascades have recently been identified and characterized, our understanding of proteins that facilitate signal transduction or assemble signaling complexes is rather sparse. Our knowledge of plant-specific remorin proteins, annotated as proteins with unknown function, has recently advanced with respect to their involvement in host–microbe interactions. Current data demonstrating that a remorin protein restricts viral movement in tomato leaves and the importance of a symbiosis-specific remorin for bacterial infection of root nodules suggest that these proteins may serve such regulatory functions. Direct interactions of other remorins with a resistance protein in Arabidopsis thaliana, and differential phosphorylation upon perception of microbial-associated molecular patterns and during expression of bacterial effector proteins, strongly underline their roles in plant defense. Furthermore, the specific subcellular localization of remorins in plasma membrane microdomains now provides the opportunity to visualize membrane rafts in living plants cells. There, remorins may oligomerize and act as scaffold proteins during early signaling events. This review summarizes current knowledge of this protein family and the potential roles of remorins in membrane rafts.

scholarly journals Glycans in Virus-Host Interactions: A Structural Perspective

2021 ◽  
Vol 8 ◽  
Author(s):  
Nathaniel L. Miller ◽  
Thomas Clark ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Immune System ◽  
Host Cells ◽  
Host Immune System ◽  
Host Interactions ◽  
Viral Glycoproteins ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Anti Hiv ◽  
Structural Perspective

Many interactions between microbes and their hosts are driven or influenced by glycans, whose heterogeneous and difficult to characterize structures have led to an underappreciation of their role in these interactions compared to protein-based interactions. Glycans decorate microbe glycoproteins to enhance attachment and fusion to host cells, provide stability, and evade the host immune system. Yet, the host immune system may also target these glycans as glycoepitopes. In this review, we provide a structural perspective on the role of glycans in host-microbe interactions, focusing primarily on viral glycoproteins and their interactions with host adaptive immunity. In particular, we discuss a class of topological glycoepitopes and their interactions with topological mAbs, using the anti-HIV mAb 2G12 as the archetypical example. We further offer our view that structure-based glycan targeting strategies are ready for application to viruses beyond HIV, and present our perspective on future development in this area.

scholarly journals Antivirulence Activity of the Human Gut Metabolome

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
L. Caetano M. Antunes ◽  
Julie A. K. McDonald ◽  
Kathleen Schroeter ◽  
Christian Carlucci ◽  
Rosana B. R. Ferreira ◽  
...  
Keyword(s):  
Small Molecules ◽  
Chemical Cues ◽  
Therapeutic Potential ◽  
Host Cells ◽  
Human Gut ◽  
Complex Ecosystem ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions

ABSTRACTThe mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor ofSalmonellavirulence, obliterating expression of theSalmonellapathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential.IMPORTANCEMicrobes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication.

The Use of High Pressure Freezing and Freeze Substitution to Study Host–Pathogen Interactions in Fungal Diseases of Plants

2003 ◽  
Vol 9 (6) ◽  
pp. 522-531 ◽  
Author(s):  
C.W. Mims ◽  
Gail J. Celio ◽  
Elizabeth A. Richardson
Keyword(s):  
High Pressure ◽  
Cell Walls ◽  
Freeze Substitution ◽  
Fungal Diseases ◽  
Host Cells ◽  
High Pressure Freezing ◽  
Plant Interactions ◽  
Host Pathogen Interactions ◽  
Thin Sections ◽  
Host Pathogen

This article reports on the use of high pressure freezing followed by freeze substitution (HPF/FS) to study ultrastructural details of host–pathogen interactions in fungal diseases of plants. The specific host–pathogen systems discussed here include a powdery mildew infection of poinsettia and rust infections of daylily and Indian strawberry. The three pathogens considered here all attack the leaves of their hosts and produce specialized hyphal branches known as haustoria that invade individual host cells without killing them. We found that HPF/FS provided excellent preservation of both haustoria and host cells for all three host–pathogen systems. Preservation of fungal and host cell membranes was particularly good and greatly facilitated the detailed study of host–pathogen interfaces. In some instances, HPF/FS provided information that was not available in samples prepared for study using conventional chemical fixation. On the other hand, we did encounter various problems associated with the use of HPF/FS. Examples included freeze damage of samples, inconsistency of fixation in different samples, separation of plant cell cytoplasm from cell walls, breakage of cell walls and membranes, and splitting of thin sections. However, we believe that the outstanding preservation of ultrastructural details afforded by HPF/FS significantly outweighs these problems and we highly recommend the use of this fixation protocol for future studies of fungal host-plant interactions.

scholarly journals Fucose Ameliorates Tritrichomonas sp.-Associated Illness in Antibiotic-Treated Muc2−/− Mice

2021 ◽  
Vol 22 (19) ◽  
pp. 10699
Author(s):  
Kseniya M. Achasova ◽  
Elena N. Kozhevnikova ◽  
Mariya A. Borisova ◽  
Ekaterina A. Litvinova
Keyword(s):  
Chronic Inflammation ◽  
Close Contact ◽  
Critical Role ◽  
Host Cells ◽  
Mucus Layer ◽  
Gene Encoding ◽  
Protozoan Infection ◽  
Bowel Diseases ◽  
Microbe Interactions ◽  
Host Microbe Interactions

The mucus layer in the intestine plays a critical role in regulation of host–microbe interactions and maintaining homeostasis. Disruptions of the mucus layer due to genetic, environmental, or immune factors may lead to inflammatory bowel diseases (IBD). IBD frequently are accompanied with infections, and therefore are treated with antibiotics. Hence, it is important to evaluate risks of antibiotic treatment in individuals with vulnerable gut barrier and chronic inflammation. Mice with a knockout of the Muc2 gene, encoding the main glycoprotein component of the mucus, demonstrate a close contact of the microbes with the gut epithelium which leads to chronic inflammation resembling IBD. Here we demonstrate that the Muc2−/− mice harboring a gut protozoan infection Tritrichomonas sp. are susceptible to an antibiotic-induced depletion of the bacterial microbiota. Suppression of the protozoan infection with efficient metronidazole dosage or L-fucose administration resulted in amelioration of an illness observed in antibiotic-treated Muc2−/− mice. Fucose is a monosaccharide presented abundantly in gut glycoproteins, including Mucin2, and is known to be involved in host–microbe interactions, in particular in microbe adhesion. We suppose that further investigation of the role of fucose in protozoan adhesion to host cells may be of great value.

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