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 ◽  
...  

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.

2018 ◽  
Vol 201 (2) ◽  
Author(s):  
Valentina Godovikova ◽  
M. Paula Goetting-Minesky ◽  
John C. Timm ◽  
J. Christopher Fenno

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.


2016 ◽  
Author(s):  
Fiona Wanjiku Moejes ◽  
Ovidiu Popa ◽  
Antonella Succurro ◽  
Julie Maguire ◽  
Oliver Ebenhöh

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.


2009 ◽  
Vol 4 (10) ◽  
pp. 457-462 ◽  
Author(s):  
Sebastian Fraune ◽  
Thomas C. G. Bosch ◽  
René Augustin

2021 ◽  
Author(s):  
Manoj Reddy Medapati ◽  
Anjali Y. Bhagirath ◽  
Nisha Singh ◽  
Prashen Chelikani

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 999
Author(s):  
Sue E. Crawford ◽  
Sasirekha Ramani ◽  
Sarah E. Blutt ◽  
Mary K. Estes

Historically, knowledge of human host–enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host–microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.


Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jack Jansma ◽  
Sahar El Aidy

AbstractThe human gut harbors an enormous number of symbiotic microbes, which is vital for human health. However, interactions within the complex microbiota community and between the microbiota and its host are challenging to elucidate, limiting development in the treatment for a variety of diseases associated with microbiota dysbiosis. Using in silico simulation methods based on flux balance analysis, those interactions can be better investigated. Flux balance analysis uses an annotated genome-scale reconstruction of a metabolic network to determine the distribution of metabolic fluxes that represent the complete metabolism of a bacterium in a certain metabolic environment such as the gut. Simulation of a set of bacterial species in a shared metabolic environment can enable the study of the effect of numerous perturbations, such as dietary changes or addition of a probiotic species in a personalized manner. This review aims to introduce to experimental biologists the possible applications of flux balance analysis in the host-microbiota interaction field and discusses its potential use to improve human health.


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