title: Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways.
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.
authors.affiliation: Systems and Translational Sciences Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, 27709, USA. nmortensen@rti.org.
authors.forename: Ninell P
authors.initials: NP
authors.lastname: Mortensen
authors.affiliation: Systems and Translational Sciences Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, 27709, USA.|NIH Eastern Regional Comprehensive Metabolomics Resource Core, Systems and Translational Sciences, RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Mercier
authors.affiliation: Systems and Translational Sciences Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, 27709, USA.|NIH Eastern Regional Comprehensive Metabolomics Resource Core, Systems and Translational Sciences, RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: McRitchie
authors.affiliation: Systems and Translational Sciences Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, 27709, USA.|NIH Eastern Regional Comprehensive Metabolomics Resource Core, Systems and Translational Sciences, RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors.forename: Tammy B
authors.initials: TB
authors.lastname: Cavallo
authors.affiliation: Systems and Translational Sciences Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, 27709, USA.|NIH Eastern Regional Comprehensive Metabolomics Resource Core, Systems and Translational Sciences, RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors.forename: Wimal
authors.initials: W
authors.lastname: Pathmasiri
authors.affiliation: Systems and Translational Sciences Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, 27709, USA.|NIH Eastern Regional Comprehensive Metabolomics Resource Core, Systems and Translational Sciences, RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA.
authors.forename: Delisha
authors.initials: D
authors.lastname: Stewart
authors.affiliation: Systems and Translational Sciences Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, 27709, USA. ssumner@rti.org.|NIH Eastern Regional Comprehensive Metabolomics Resource Core, Systems and Translational Sciences, RTI International, 3040 East Cornwallis Road, Research Triangle Park, NC, 27709-2194, USA. ssumner@rti.org.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Sumner
mesh_terms: D001422:Bacterial Adhesion; D018938:Caco-2 Cells; D002169:Campylobacter Infections / Q000175:diagnosis*; D016123:Campylobacter jejuni / Q000472:pathogenicity*; D006801:Humans; D055432:Metabolomics; D044085:Microfluidics / Q000295:instrumentation*
keywords: Caco-2 cells; Campylobacter jejuni; Host-pathogen interaction; Infectious disease model; Metabolomics; Microfluidic