Catabolite repression by intracellular succinate in Campylobacter jejuni

Authors: VAN DER STEL, ANNE–XANDER - Utrecht University; VAN DE LEST, CHRIS - Utrecht University; Huynh, Steven; Parker, Craig; VAN PUTTEN, JOS P. - Utrecht University; WÖSTEN, MARE - Utrecht University

Submitted to: Environmental Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2018
Publication Date: 2/2/2018
Citation: Van Der Stel, A., Van De Lest, C.H., Huynh, S., Parker, C., Van Putten, J.M., Wösten, M.M. 2018. Catabolite repression by intracellular succinate in Campylobacter jejuni. Environmental Microbiology. https://doi.org/10.1111/1462-2920.14042.
DOI: https://doi.org/10.1111/1462-2920.14042

Interpretive Summary: Campylobacter jejuni is an important human pathogen. Unlike other bacteria, C. jejuni does not metabolize sugars, but relies on amino acids for growth. In order to survive in the gut and cause pathogenicity this bacterium must adjust its metabolism to the available nutrients, so that it can outcompete the other microbiota. To date, little information is known about the strategies and mechanisms that C. jejuni uses to regulate its metabolism. In this article, we describe how C. jejuni adjust its metabolism towards favorable nutrients present in its environment. Our results suggest that C. jejuni uses the accumulation of the intracellular metabolite succinate as a cue to adjust the gene expression of metabolic enzymes, so that it can make optimal use of the available nutrients. Bacteria have evolved different mechanisms to catabolize carbon sources from a mixture of nutrients. They first consume their preferred carbon source, before others are used. Regulatory mechanisms adapt the metabolism accordingly to maximize growth and to outcompete other organisms. The human pathogen Campylobacter jejuni is an asaccharolytic Gram-negative bacterium that catabolizes amino acids and organic acids for growth. It prefers serine and aspartate as carbon sources, however it lacks all regulators known to be involved in regulating carbon source utilization in other organisms. In which manner C. jejuni adapts its metabolism towards the presence or absence of preferred carbon sources is unknown. In this study, we show with transcriptomic analysis and enzyme assays how C. jejuni adapts its metabolism in response to its preferred carbon source serine. In the presence of serine as well as lactate and pyruvate C. jejuni represses the utilization of other carbon sources, by repressing the expression of a number of central metabolic enzymes. The regulatory proteins RacR, Cj1000 and CsrA play a role in the regulation of these metabolic enzymes. This metabolism dependent transcriptional repression correlates with an accumulation of intracellular succinate. Hence, we propose a demand-based catabolite repression mechanism in C. jejuni, which depends on the intracellular succinate level.

Technical Abstract: Bacteria have evolved different mechanisms to catabolize carbon sources from a mixture of nutrients. They first consume their preferred carbon source, before others are used. Regulatory mechanisms adapt the metabolism accordingly to maximize growth and to outcompete other organisms. The human pathogen Campylobacter jejuni is an asaccharolytic Gram-negative bacterium that catabolizes amino acids and organic acids for growth. It prefers serine and aspartate as carbon sources, however it lacks all regulators known to be involved in regulating carbon source utilization in other organisms. In which manner C. jejuni adapts its metabolism towards the presence or absence of preferred carbon sources is unknown. In this study, we show with transcriptomic analysis and enzyme assays how C. jejuni adapts its metabolism in response to its preferred carbon source serine. In the presence of serine as well as lactate and pyruvate C. jejuni represses the utilization of other carbon sources, by repressing the expression of a number of central metabolic enzymes. The regulatory proteins RacR, Cj1000 and CsrA play a role in the regulation of these metabolic enzymes. This metabolism dependent transcriptional repression correlates with an accumulation of intracellular succinate. Hence, we propose a demand-based catabolite repression mechanism in C. jejuni, which depends on the intracellular succinate level. Campylobacter jejuni is an important human pathogen. Unlike other bacteria, C. jejuni does not metabolize sugars, but relies on amino acids for growth. In order to survive in the gut and cause pathogenicity this bacterium must adjust its metabolism to the available nutrients, so that it can outcompete the other microbiota. To date, little information is known about the strategies and mechanisms that C. jejuni uses to regulate its metabolism. In this article, we describe how C. jejuni adjust its metabolism towards favorable nutrients present in its environment. Our results suggest that C. jejuni uses the accumulation of the intracellular metabolite succinate as a cue to adjust the gene expression of metabolic enzymes, so that it can make optimal use of the available nutrients.