Catabolite repression in Campylobacter jejuni correlates with intracellular succinate levels

Abstract

Bacteria have evolved different mechanisms to catabolize carbon sources from nutrient mixtures. 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 sources. In the presence of serine as well as lactate and pyruvate C. jejuni inhibits 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, depended on intracellular succinate levels.

Proteomics Reveals Multiple Phenotypes Associated with N-linked Glycosylation in Campylobacter jejuni

“…Deletion of succinate dehydrogenase activity encoded by FrdABC leads to an inability to use Glu and Pro, as well as a colonization deficit in chickens (51). Accumulation of intracellular succinate has been observed as a correlating factor in catabolite repression and associated with the transcription factors RacRS, Cj1000 and CsrA (67). Neither RacRS or CsrA were differentially regulated in our data set, whereas Cj1000 was significantly downregulated, suggesting intracellular succinate accumulation was unrelated to this phenomenon.…”

Regulation of Respiratory Pathways in Campylobacterota: A Review

“…These regulatory systems are widely distributed and conserved in the Proteobacteria, but not in the Campylobacterota (formerly Epsilonproteobacteria) (Leyn et al, 2016). Genome and mutagenesis analyses indicate that the genes encoding these and other well-studied regulators are lacking in the genomes of Campylobacterota (Tomb et al, 1997; Parkhill et al, 2000; Baar et al, 2003; Miller et al, 2007; Sievert et al, 2008; Goris et al, 2014; De la Cruz et al, 2017; van der Stel et al, 2018). Campylobacterota have relatively small genomes compared to other bacteria and consequently a scaled down number of regulatory proteins (Galperin, 2006).…”

Optimizing microbiome sequencing for small intestinal aspirates: validation of novel techniques through the REIMAGINE study

“…The phylum Proteobacteria also includes aerotolerant asaccharolytic microorganisms that require proteinaceous substrates as carbon and energy sources, such as Campylobacter [26], as well as facultative anaerobes from the family Enterobacteriaceae included in the "Mucosally Associated Consortium" in the colon described by Albenberg et al [24]. Pretreatment of DA with DTT increases the detected relative abundance of many Enterobacteriaceae members, including the clinically important genera Klebsiella, Providencia and Salmonella as well as unknown members.…”