Campylobacter jejuni demonstrates conserved proteomic and transcriptomic responses when co-cultured with human INT 407 and Caco-2 epithelial cells

Authors: NEGRETTI, NICHOLAS - Washington State University; CLAIR, GEREMY - Pacific Northwest National Laboratory; GOURLEY, CHRISTOPHER - Washington State University; Huynh, Steven; ADKINS, JOSHUA - Pacific Northwest National Laboratory; Parker, Craig; KONKEL, MICHAEL - Washington State University

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/26/2019
Publication Date: 4/11/2019
Citation: Negretti, N.M., Clair, G., Gourley, C.R., Huynh, S., Adkins, J.N., Parker, C., Konkel, M.E. 2019. Campylobacter jejuni demonstrates conserved proteomic and transcriptomic responses when co-cultured with human INT 407 and Caco-2 epithelial cells. Frontiers in Microbiology. 10:755. https://doi.org/10.3389/fmicb.2019.00755.
DOI: https://doi.org/10.3389/fmicb.2019.00755

Interpretive Summary: Pathogens must navigate a gauntlet of hostile host environments and defenses to eventually cause disease in the human intestine. These ever changing host conditions encountered by bacteria when they are ingested and passed through the alimentary canal provide stress stimuli to bacteria, giving them cues to alter their behavior for enhanced survival. Major foodborne bacterial pathogens, such as Campylobacter jejuni, have devised complex strategies to establish and foster intestinal infections. For more than two decades researchers have used immortalized cell lines derived from human intestinal tissue to dissect C. jejuni-host cell interactions. Known from these studies is that C. jejuni virulence is multifactorial, requiring a coordinated response to produce virulence factors that facilitate the bacterium’s survival in the host. This study was initiated to identify C. jejuni proteins that contribute to bacteria-host cell interactions. We demonstrated that C. jejuni responds to INT 407 and Caco-2 cells in a similar fashion at the cellular and molecular levels. Active protein synthesis was found to be required for C. jejuni to maximally invade these host cells. An omics approach was then used to define the protein and gene expression profiles of C. jejuni co-cultured with cells. These studies revealed that C. jejuni actively seek to acquire nutrients and iron, while resisting the toxic effects of reactive oxygen/nitrogen species. Known C. jejuni virulence genes and genes encoding products not previously recognized as contributing to pathogenesis were found to be upregulated after co-culture with host cells. This study demonstrates that C. jejuni quickly adapts to co-culture with epithelial cells to express gene products that enable it to acquire nutrients, scavenge for inorganic molecules, resist reactive oxygen/nitrogen species, and invade host epithelial cells. The identification of these genes involved in C. jejuni adaptation to culture with host cells provides new insights into the infection process.

Technical Abstract: Major foodborne bacterial pathogens, such as Campylobacter jejuni, have devised complex strategies to establish and foster intestinal infections. For more than two decades researchers have used immortalized cell lines derived from human intestinal tissue to dissect C. jejuni-host cell interactions. Known from these studies is that C. jejuni virulence is multifactorial, requiring a coordinated response to produce virulence factors that facilitate the bacterium’s survival in the host. This study was initiated to identify C. jejuni proteins that contribute to bacteria-host cell interactions. We demonstrated that C. jejuni responds to INT 407 and Caco-2 cells in a similar fashion at the cellular and molecular levels. Active protein synthesis was found to be required for C. jejuni to maximally invade these host cells. An omics approach was then used to define the protein and gene expression profiles of C. jejuni co-cultured with cells. These studies revealed that C. jejuni actively seek to acquire nutrients and iron, while resisting the toxic effects of reactive oxygen/nitrogen species. Known C. jejuni virulence genes and genes encoding products not previously recognized as contributing to pathogenesis were found to be upregulated after co-culture with host cells. This study demonstrates that C. jejuni quickly adapts to co-culture with epithelial cells to express gene products that enable it to acquire nutrients, scavenge for inorganic molecules, resist reactive oxygen/nitrogen species, and invade host epithelial cells. The identification of these genes involved in C. jejuni adaptation to culture with host cells provides new insights into the infection process.