Spatial metabolomics of in situ, host-microbe interactions

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.

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Microbial interactions in the mosquito gut determine Serratia colonization and blood-feeding propensity

The ISME Journal ◽

10.1038/s41396-020-00763-3 ◽

2020 ◽

Vol 15 (1) ◽

pp. 93-108

Author(s):

Elena V. Kozlova ◽

Shivanand Hegde ◽

Christopher M. Roundy ◽

George Golovko ◽

Miguel A. Saldaña ◽

...

Keyword(s):

Vector Competence ◽

Inverse Correlation ◽

Blood Feeding ◽

Microbial Interactions ◽

Host Behavior ◽

Microbiome Analysis ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Native Host ◽

Mosquito Behavior

AbstractHow microbe–microbe interactions dictate microbial complexity in the mosquito gut is unclear. Previously we found that, Serratia, a gut symbiont that alters vector competence and is being considered for vector control, poorly colonized Aedes aegypti yet was abundant in Culex quinquefasciatus reared under identical conditions. To investigate the incompatibility between Serratia and Ae. aegypti, we characterized two distinct strains of Serratia marcescens from Cx. quinquefasciatus and examined their ability to infect Ae. aegypti. Both Serratia strains poorly infected Ae. aegypti, but when microbiome homeostasis was disrupted, the prevalence and titers of Serratia were similar to the infection in its native host. Examination of multiple genetically diverse Ae. aegypti lines found microbial interference to S. marcescens was commonplace, however, one line of Ae. aegypti was susceptible to infection. Microbiome analysis of resistant and susceptible lines indicated an inverse correlation between Enterobacteriaceae bacteria and Serratia, and experimental co-infections in a gnotobiotic system recapitulated the interference phenotype. Furthermore, we observed an effect on host behavior; Serratia exposure to Ae. aegypti disrupted their feeding behavior, and this phenotype was also reliant on interactions with their native microbiota. Our work highlights the complexity of host–microbe interactions and provides evidence that microbial interactions influence mosquito behavior.

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

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-07-10-0166 ◽

2011 ◽

Vol 24 (1) ◽

pp. 7-12 ◽

Cited By ~ 75

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.

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Glycans in Virus-Host Interactions: A Structural Perspective

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.666756 ◽

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.

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Bridging the Gap Between Single-Strain and Community-Level Plant-Microbe Chemical Interactions

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-04-19-0115-cr ◽

2020 ◽

Vol 33 (2) ◽

pp. 124-134 ◽

Cited By ~ 7

Author(s):

Bridget S. O’Banion ◽

Lindsey O’Neal ◽

Gladys Alexandre ◽

Sarah L. Lebeis

Keyword(s):

Chemical Exchange ◽

Chemical Signals ◽

Individual Plant ◽

Single Strain ◽

Plant Hosts ◽

Culture Independent ◽

Microbe Interactions ◽

Tools And Techniques ◽

Insight Into

Although the influence of microbiomes on the health of plant hosts is evident, specific mechanisms shaping the structure and dynamics of microbial communities in the phyllosphere and rhizosphere are only beginning to become clear. Traditionally, plant–microbe interactions have been studied using cultured microbial isolates and plant hosts but the rising use of ‘omics tools provides novel snapshots of the total complex community in situ. Here, we discuss the recent advances in tools and techniques used to monitor plant–microbe interactions and the chemical signals that influence these relationships in above- and belowground tissues. Particularly, we highlight advances in integrated microscopy that allow observation of the chemical exchange between individual plant and microbial cells, as well as high-throughput, culture-independent approaches to investigate the total genetic and metabolic contribution of the community. The chemicals discussed have been identified as relevant signals across experimental spectrums. However, mechanistic insight into the specific interactions mediated by many of these chemicals requires further testing. Experimental designs that attempt to bridge the gap in biotic complexity between single strains and whole communities will advance our understanding of the chemical signals governing plant–microbe associations in the rhizosphere and phyllosphere.

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Antivirulence Activity of the Human Gut Metabolome

mBio ◽

10.1128/mbio.01183-14 ◽

2014 ◽

Vol 5 (4) ◽

Cited By ~ 31

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.

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Spatial Analyses of Specialized Metabolites: The Key to Studying Function in Hosts

mSystems ◽

10.1128/msystems.00148-17 ◽

2018 ◽

Vol 3 (2) ◽

Cited By ~ 4

Author(s):

Melissa M. Galey ◽

Laura M. Sanchez

Keyword(s):

Analytical Chemistry ◽

Molecular Mechanisms ◽

Imaging Mass Spectrometry ◽

Analytical Techniques ◽

Spatial Analyses ◽

Biological Functions ◽

Specialized Metabolites ◽

Microbe Interactions ◽

Host Microbe Interactions

ABSTRACT Microbial communities contribute to a wide variety of biological functions in hosts and have the ability to specifically influence the health of those organisms through production of specialized metabolites. However, the structures or molecular mechanisms related to health or disease in host-microbe interactions represent a knowledge gap. In order to close this gap, we propose that a combinatory approach, pulling from microbiology and analytical chemistry, be considered to investigate these interactions so as to gain a better understanding of the chemistry being produced. We hypothesize that bacteria alter their chemistry in order to survive and induce specific states in their host organisms. Our lab makes use of imaging mass spectrometry and other analytical techniques to study this chemistry in situ , which provides actionable information to test hypotheses.

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Metagenomic and Metatranscriptomic Analyses Reveal the Structure and Dynamics of a Dechlorinating Community Containing Dehalococcoides mccartyi and Corrinoid-Providing Microorganisms under Cobalamin-Limited Conditions

Applied and Environmental Microbiology ◽

10.1128/aem.03508-16 ◽

2017 ◽

Vol 83 (8) ◽

Cited By ~ 17

Author(s):

Yujie Men ◽

Ke Yu ◽

Jacob Bælum ◽

Ying Gao ◽

Julien Tremblay ◽

...

Keyword(s):

De Novo ◽

Early Stage ◽

Microbial Interactions ◽

Community Members ◽

Content Type ◽

Dehalococcoides Mccartyi ◽

Level Information ◽

Microbe Interactions ◽

The One ◽

Shed Light

ABSTRACT The aim of this study is to obtain a systems-level understanding of the interactions between Dehalococcoides and corrinoid-supplying microorganisms by analyzing community structures and functional compositions, activities, and dynamics in trichloroethene (TCE)-dechlorinating enrichments. Metagenomes and metatranscriptomes of the dechlorinating enrichments with and without exogenous cobalamin were compared. Seven putative draft genomes were binned from the metagenomes. At an early stage (2 days), more transcripts of genes in the Veillonellaceae bin-genome were detected in the metatranscriptome of the enrichment without exogenous cobalamin than in the one with the addition of cobalamin. Among these genes, sporulation-related genes exhibited the highest differential expression when cobalamin was not added, suggesting a possible release route of corrinoids from corrinoid producers. Other differentially expressed genes include those involved in energy conservation and nutrient transport (including cobalt transport). The most highly expressed corrinoid de novo biosynthesis pathway was also assigned to the Veillonellaceae bin-genome. Targeted quantitative PCR (qPCR) analyses confirmed higher transcript abundances of those corrinoid biosynthesis genes in the enrichment without exogenous cobalamin than in the enrichment with cobalamin. Furthermore, the corrinoid salvaging and modification pathway of Dehalococcoides was upregulated in response to the cobalamin stress. This study provides important insights into the microbial interactions and roles played by members of dechlorinating communities under cobalamin-limited conditions. IMPORTANCE The key chloroethene-dechlorinating bacterium Dehalococcoides mccartyi is a cobalamin auxotroph, thus acquiring corrinoids from other community members. Therefore, it is important to investigate the microbe-microbe interactions between Dehalococcoides and the corrinoid-providing microorganisms in a community. This study provides systems-level information, i.e., taxonomic and functional compositions and dynamics of the supportive microorganisms in dechlorinating communities under different cobalamin conditions. The findings shed light on the important roles of Veillonellaceae species in the communities compared to other coexisting community members in producing and providing corrinoids for Dehalococcoides species under cobalamin-limited conditions.

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

International Journal of Molecular Sciences ◽

10.3390/ijms221910699 ◽

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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Microbial interactions in the mosquito gut determine Serratia colonization and blood feeding propensity.

10.1101/2020.04.14.039701 ◽

2020 ◽

Author(s):

Elena V Kozlova ◽

Shivanand Hegde ◽

Christopher M Roundy ◽

George Golovko ◽

Miguel A Saldana ◽

...

Keyword(s):

Vector Competence ◽

Inverse Correlation ◽

Blood Feeding ◽

Microbial Interactions ◽

Microbiome Analysis ◽

Mosquito Behaviour ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Host Behaviour ◽

Native Host

How microbe-microbe interactions dictate microbial complexity in the mosquito gut is unclear. Previously we found that Serratia, a gut symbiont that alters vector competence and is being considered for vector control, poorly colonized Aedes aegypti yet was abundant in Culex quinquefasciatus reared under identical conditions. To investigate the incompatibility between Serratia and Ae. aegypti, we characterized two distinct strains of Serratia marcescens from Cx. quinquefasciatus and examined their ability to infect Ae. aegypti. Both Serratia strains poorly infected Ae. aegypti, but when microbiome homeostasis was disrupted, the prevalence and titers of Serratia were similar to the infection in its native host. Examination of multiple genetically diverse Ae. aegypti lines found microbial interference to S. marcescens was commonplace, however one line of Ae. aegypti was susceptible to infection. Microbiome analysis of resistant and susceptible lines indicated an inverse correlation between Enterobacteriaceae bacteria and Serratia, and experimental co-infections in a gnotobiotic system recapitulated the interference phenotype. Furthermore, we observed an effect on host behaviour; Serratia exposure to Ae. aegypti disrupted their feeding behaviour, and this phenotype was also reliant on interactions with their native microbiota. Our work highlights the complexity of host-microbe interactions and provides evidence that microbial interactions influence mosquito behaviour.

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