scholarly journals Immunotopological Analysis of theTreponema denticolaMajor Surface Protein (Msp)

2018 ◽  
Vol 201 (2) ◽  
Author(s):  
Valentina Godovikova ◽  
M. Paula Goetting-Minesky ◽  
John C. Timm ◽  
J. Christopher Fenno
Keyword(s):  
Outer Membrane ◽  
In Silico ◽  
Model Organism ◽  
Surface Protein ◽  
Membrane Topology ◽  
Orthologous Group ◽  
Treponema Denticola ◽  
Functional Relationships ◽  
Microbe Interactions ◽  
Host Microbe Interactions

ABSTRACTTreponema denticola, one of several recognized periodontal pathogens, is a model organism for studyingTreponemaphysiology and host-microbe interactions. Its major surface protein Msp (or MOSP) comprises an oligomeric outer membrane-associated complex that binds fibronectin, has cytotoxic pore-forming activity, and disrupts several intracellular responses. There are two hypotheses regarding native Msp structure and membrane topology. One hypothesis predicts that the entire Msp protein forms a β-barrel structure similar to that of well-studied outer membrane porins of Gram-negative bacteria. The second hypothesis predicts a bipartite Msp with distinct and separate periplasmic N-terminal and porin-like β-barrel C-terminal domains. The bipartite model, based on bioinformatic analysis of the orthologousTreponema pallidumTpr proteins, is supported largely by studies of recombinant TprC and Msp polypeptides. The present study reports immunological studies in bothT. denticolaandEscherichia colibackgrounds to identify a prominent Msp surface epitope (residues 229 to 251 in ATCC 35405) in a domain that differs between strains with otherwise highly conserved Msps. These results were then used to evaluate a series ofin silicostructural models of representativeT. denticolaMsps. The data presented here are consistent with a model of Msp as a large-diameter β-barrel porin. This work adds to the knowledge regarding the diverse Msp-like proteins in oral treponemes and may contribute to an understanding of the evolutionary and potential functional relationships between Msps of oralTreponemaand the orthologous group of Tpr proteins ofT. pallidum.IMPORTANCETreponema denticolais among a small subset of the oral microbiota contributing to severe periodontal disease. Due to its relative genetic tractability,T. denticolais a model organism for studyingTreponemaphysiology and host-microbe interactions.T. denticolaMsp is a highly expressed outer membrane-associated oligomeric protein that binds fibronectin, has cytotoxic pore-forming activity, and disrupts intracellular regulatory pathways. It shares homology with the orthologous group ofT. pallidumTpr proteins, one of which is implicated inT. pallidum in vivoantigenic variation. The outer membrane topologies of both Msp and the Tpr family proteins are unresolved, with conflicting reports on protein domain localization and function. In this study, we combined empirical immunological data derived both from diverseT. denticolastrains and from recombinant Msp expression inE. coliwithin silicopredictive structural modeling ofT. denticolaMsp membrane topology, to move toward resolution of this important issue inTreponemabiology.

scholarly journals Mammalian lectin arrays for screening host–microbe interactions

2020 ◽  
Vol 295 (14) ◽  
pp. 4541-4555 ◽  
Author(s):  
Sabine A. F. Jégouzo ◽  
Conor Nelson ◽  
Thomas Hardwick ◽  
S. T. Angel Wong ◽  
Noel Kuan Kiat Lau ◽  
...  
Keyword(s):  
Model Organism ◽  
Yeast Cells ◽  
Target Cells ◽  
Binding Studies ◽  
Lectin Array ◽  
Receptor Interactions ◽  
Microbe Interactions ◽  
Lectin Family ◽  
Host Microbe Interactions ◽  
Mammalian Lectin

Many members of the C-type lectin family of glycan-binding receptors have been ascribed roles in the recognition of microorganisms and serve as key receptors in the innate immune response to pathogens. Other mammalian receptors have become targets through which pathogens enter target cells. These receptor roles have often been documented with binding studies involving individual pairs of receptors and microorganisms. To provide a systematic overview of interactions between microbes and the large complement of C-type lectins, here we developed a lectin array and suitable protocols for labeling of microbes that could be used to probe this array. The array contains C-type lectins from cow, chosen as a model organism of agricultural interest for which the relevant pathogen–receptor interactions have not been previously investigated in detail. Screening with yeast cells and various strains of both Gram-positive and -negative bacteria revealed distinct binding patterns, which in some cases could be explained by binding to lipopolysaccharides or capsular polysaccharides, but in other cases they suggested the presence of novel glycan targets on many of the microorganisms. These results are consistent with interactions previously ascribed to the receptors, but they also highlight binding to additional sugar targets that have not previously been recognized. Our findings indicate that mammalian lectin arrays represent unique discovery tools for identifying both novel ligands and new receptor functions.

scholarly journals An internal thioester in a pathogen surface protein mediates covalent host binding

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Miriam Walden ◽  
John M Edwards ◽  
Aleksandra M Dziewulska ◽  
Rene Bergmann ◽  
Gerhard Saalbach ◽  
...  
Keyword(s):  
Covalent Binding ◽  
Surface Protein ◽  
Bacterial Attachment ◽  
Surface Proteins ◽  
Host Protein ◽  
Covalent Interaction ◽  
Gram Positive Bacteria ◽  
Thioester Bond ◽  
Microbe Interactions ◽  
Host Microbe Interactions

To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions.

scholarly journals Protective Plant Immune Responses are Elicited by Bacterial Outer Membrane Vesicles

2020 ◽  
Author(s):  
Hannah M. McMillan ◽  
Sophia G. Zebell ◽  
Jean B. Ristaino ◽  
Xinnian Dong ◽  
Meta J. Kuehn
Keyword(s):  
Immune Responses ◽  
Outer Membrane ◽  
Pseudomonas Syringae ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Plant Responses ◽  
Bacterial Survival ◽  
Microbe Interactions ◽  
Bacterial Outer Membrane ◽  
Host Microbe Interactions

SummaryBacterial outer membrane vesicles (OMVs) perform a variety of functions in bacterial survival and virulence. In mammalian systems, OMVs activate immune responses and have been exploited as vaccines. However, little work has focused on the role that OMVs play during interactions with plant hosts. Here we report that OMVs from the pathogenic Pseudomonas syringae and the beneficial Pseudomonas fluorescens activate plant immune responses that protect against bacterial and oomycete pathogens. OMVs from these two species display different sensitivity to biochemical stressors, which could indicate differences in OMV cargo packaging. Furthermore, our study shows that OMV-induced protective immune responses are T3SS- and protein-independent, while OMV-mediated seedling growth inhibition largely depends on protein cargo. Importantly, OMV-mediated plant responses are distinct from those triggered by PAMP/MAMPs or effector molecules alone. OMVs provide a unique opportunity to study virulence factors in combination and add a new layer of interaction and complexity to host-microbe interactions.

scholarly journals Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anukriti Verma ◽  
Shivani Sharda ◽  
Bhawna Rathi ◽  
Pallavi Somvanshi ◽  
Bimlesh Dhar Pandey
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Reactive Arthritis ◽  
In Silico ◽  
Molecular Signatures ◽  
Combinatorial Approach ◽  
Microbe Interactions ◽  
Inflammatory Bowel ◽  
Host Microbe Interactions

Abstract Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe ‘interspecies communication’, using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA. Our study identified Na(+)/H(+) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies.

scholarly journals Small RNAs in Outer Membrane Vesicles and Their Function in Host-Microbe Interactions

2020 ◽  
Vol 11 ◽  
Author(s):  
Sara Ahmadi Badi ◽  
Stefania Paola Bruno ◽  
Arfa Moshiri ◽  
Samira Tarashi ◽  
Seyed Davar Siadat ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Small Rnas ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Microbe Interactions ◽  
Host Microbe Interactions

scholarly journals Dynamics of the bacterial community associated withPhaeodactylum tricornutumcultures

2016 ◽  
Author(s):  
Fiona Wanjiku Moejes ◽  
Ovidiu Popa ◽  
Antonella Succurro ◽  
Julie Maguire ◽  
Oliver Ebenhöh
Keyword(s):  
Bacterial Community ◽  
Phaeodactylum Tricornutum ◽  
Large Scale ◽  
Model Organism ◽  
Interdisciplinary Approach ◽  
Pennate Diatom ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Insight Into ◽  
Over Time

AbstractThe pennate diatomPhaeodactylum tricornutumis a model organism able to synthesise industrially-relevant molecules. Large-scale monocultures are prone to bio-contamination, however, little is known about the identity of the invading organisms. To gain insight into the bacterial community associated with diatoms, we translated the complexity of a natural system into reproducible experiments where we investigated the microbiome ofP. tricornutumcultures. The results revealed a dynamic bacterial community that changed over time and in differing media conditions. We propose a network of putative interactions betweenP. tricornutumand the main bacterial factions, which is translated into a set of ordinary differential equations constituting a computational dynamic model. The proposed mathematical model is able to capture the population dynamics, further supporting the hypothesised interactions. The interdisciplinary approach implemented provides a framework for understanding the dynamics of diatom-associated microbial communities, and provides a foundation for further systematic investigations of host-microbe interactions.

scholarly journals Causal inference on microbiome-metabolome relations via in silico in vivo association pattern analyses

2021 ◽  
Author(s):  
Johannes Hertel ◽  
Almut Heinken ◽  
Ines Thiele
Keyword(s):  
Causal Inference ◽  
In Silico ◽  
Association Studies ◽  
New Paradigm ◽  
Association Pattern ◽  
Knowledge Based ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions

The effects of the microbiome on the host's metabolism are core to understanding the role of the microbiome in health and disease. Herein, we develop the paradigm of in silico in vivo association pattern analyses, entailing a methodology to combine microbiome metabolome association studies with in silico constraint-based microbial community modelling. By dissecting confounding and causal paths, we show that in silico in vivo association pattern analyses allows for causal inference on microbiome-metabolome relations in observational data. Then, we demonstrate the feasibility and validity of our approach on a published multi-omics dataset (n=346), demonstrating causal microbiome-metabolite relations for 43 out of 53 metabolites from faeces. Finally, we utilise the identified in silico in vivo association pattern to estimate the microbial component of the faecal metabolome, revealing that the retrieved metabolite prediction scores correlate with the measured metabolite concentrations, and they also reflect the multivariate structure of the faecal metabolome. Concluding, we integrate with hypothesis-free screening association studies and knowledge-based in silico modelling two major paradigms of systems biology, generating a promising new paradigm for causal inference in metabolic host-microbe interactions.

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