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Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways

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Abstract

Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81–176 for 48 h. Metabolomics analysis clearly differentiated C. jejuni 81–176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81–176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time.

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Acknowledgments

This study was supported by RTI International internal research funding and National Institute of Diabetes and Digestive and Kidney Diseases (1U24DK097193-01, Dr. Susan Sumner, PI). The authors are grateful to Andrew Novokhatny and Zachery Acuff for providing analytical and statistical assistance with the metabolomics data analysis. The metabolomics data are available at the NIH Common Fund Metabolomics Data Repository and Coordinating Center at the University of California at San Diego (Dr. Shankar Subramaniam, PI) under studies ST000124 and ST000125.

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  1. Systems and Translational Sciences Discovery – Science – Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, 27709, USA

    Ninell P. Mortensen, Kelly A. Mercier, Susan McRitchie, Tammy B. Cavallo, Wimal Pathmasiri, Delisha Stewart & Susan J. Sumner

  2. NIH Eastern Regional Comprehensive Metabolomics Resource Core, Systems and Translational Sciences, RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA

    Kelly A. Mercier, Susan McRitchie, Tammy B. Cavallo, Wimal Pathmasiri, Delisha Stewart & Susan J. Sumner

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  1. Ninell P. Mortensen
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Correspondence to Ninell P. Mortensen or Susan J. Sumner.

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Mortensen, N.P., Mercier, K.A., McRitchie, S. et al. Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways. Biomed Microdevices 18, 51 (2016). https://doi.org/10.1007/s10544-016-0076-9

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