Uncovering complex molecular networks in host–pathogen interactions using systems biology

Abstract Interactions between pathogens and their hosts can induce complex changes in both host and pathogen states to privilege pathogen survival or host clearance of the pathogen. To determine the consequences of specific host–pathogen interactions, a variety of techniques in microbiology, cell biology, and immunology are available to researchers. Systems biology that enables unbiased measurements of transcriptomes, proteomes, and other biomolecules has become increasingly common in the study of host–pathogen interactions. These approaches can be used to generate novel hypotheses or to characterize the effects of particular perturbations across an entire biomolecular network. With proper experimental design and complementary data analysis tools, high-throughput omics techniques can provide novel insights into the mechanisms that underlie processes from phagocytosis to pathogen immune evasion. Here, we provide an overview of the suite of biochemical approaches for high-throughput analyses of host–pathogen interactions, analytical frameworks for understanding the resulting datasets, and a vision for the future of this exciting field.

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High-Throughput Microfluidic Method To Study Biofilm Formation and Host-Pathogen Interactions in Pathogenic Escherichia coli

Applied and Environmental Microbiology ◽

10.1128/aem.04208-14 ◽

2015 ◽

Vol 81 (8) ◽

pp. 2827-2840 ◽

Cited By ~ 16

Author(s):

Yannick D. N. Tremblay ◽

Philippe Vogeleer ◽

Mario Jacques ◽

Josée Harel

Keyword(s):

Escherichia Coli ◽

High Throughput ◽

Biofilm Formation ◽

Cell Biology ◽

Shear Force ◽

Host Pathogen Interactions ◽

Content Type ◽

E Coli ◽

Rpmi Medium ◽

Host Pathogen

ABSTRACTBiofilm formation and host-pathogen interactions are frequently studied using multiwell plates; however, these closed systems lack shear force, which is present at several sites in the host, such as the intestinal and urinary tracts. Recently, microfluidic systems that incorporate shear force and very small volumes have been developed to provide cell biology models that resemblein vivoconditions. Therefore, the objective of this study was to determine if the BioFlux 200 microfluidic system could be used to study host-pathogen interactions and biofilm formation by pathogenicEscherichia coli. Strains of various pathotypes were selected to establish the growth conditions for the formation of biofilms in the BioFlux 200 system on abiotic (glass) or biotic (eukaryotic-cell) surfaces. Biofilm formation on glass was observed for the majority of strains when they were grown in M9 medium at 30°C but not in RPMI medium at 37°C. In contrast, HRT-18 cell monolayers enhanced binding and, in most cases, biofilm formation by pathogenicE. coliin RPMI medium at 37°C. As a proof of principle, the biofilm-forming ability of a diffusely adherentE. colimutant strain lacking AIDA-I, a known mediator of attachment, was assessed in our models. In contrast to the parental strain, which formed a strong biofilm, the mutant formed a thin biofilm on glass or isolated clusters on HRT-18 monolayers. In conclusion, we describe a microfluidic method for high-throughput screening that could be used to identify novel factors involved inE. colibiofilm formation and host-pathogen interactions under shear force.

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Plasmodium vivax Cell Traversal Protein for Ookinetes and Sporozoites (CelTOS) Functionally Restricted Regions Are Involved in Specific Host-Pathogen Interactions

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.00119 ◽

2020 ◽

Vol 10 ◽

Author(s):

Gabriela Arévalo-Pinzón ◽

Diego Garzón-Ospina ◽

Fredy A. Pulido ◽

Maritza Bermúdez ◽

Johanna Forero-Rodríguez ◽

...

Keyword(s):

Plasmodium Vivax ◽

Host Pathogen Interactions ◽

Specific Host ◽

Host Pathogen

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Highly specific host-pathogen interactions influence Metarhizium brunneum blastospore virulence against Culex quinquefasciatus larvae

Virulence ◽

10.1080/21505594.2018.1509665 ◽

2018 ◽

Vol 9 (1) ◽

pp. 1449-1467 ◽

Cited By ~ 6

Author(s):

Abeer M. Alkhaibari ◽

Alex M. Lord ◽

Thierry Maffeis ◽

James C. Bull ◽

Fabio L. Olivares ◽

...

Keyword(s):

Culex Quinquefasciatus ◽

Host Pathogen Interactions ◽

Metarhizium Brunneum ◽

Specific Host ◽

Host Pathogen

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Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model

BMC Genomics ◽

10.1186/s12864-019-6269-x ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Jonas Kjellin ◽

Maria Pränting ◽

Frauke Bach ◽

Roshan Vaid ◽

Bart Edelbroek ◽

...

Keyword(s):

Dictyostelium Discoideum ◽

High Throughput ◽

Legionella Pneumophila ◽

Transcriptional Response ◽

Infection Model ◽

Intracellular Pathogens ◽

Host Pathogen Interactions ◽

Human Macrophages ◽

Wide Range ◽

Host Pathogen

Abstract Background During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages. Results The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila. Conclusions Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.

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