Glucose Metabolism via the Entner-Doudoroff Pathway in Campylobacter: A Rare Trait that Enhances Survival and Promotes Biofilm Formation in Some Isolates

Abstract

Isolates of the zoonotic pathogen Campylobacter are generally considered to be unable to metabolize glucose due to lack of key glycolytic enzymes. However, the Entner-Doudoroff (ED) pathway has been identified in Campylobacter jejuni subsp. doylei and a few C. coli isolates. A systematic search for ED pathway genes in a wide range of Campylobacter isolates and in the C. jejuni/coli PubMLST database revealed that 1.7% of >6,000 genomes encoded a complete ED pathway, including both C. jejuni and C. coli from diverse clinical, environmental and animal sources. In rich media, glucose significantly enhanced stationary phase survival of a set of ED-positive C. coli isolates. Unexpectedly, glucose massively promoted floating biofilm formation in some of these ED-positive isolates. Metabolic profiling by gas chromatography–mass spectrometry revealed distinct responses to glucose in a low biofilm strain (CV1257) compared to a high biofilm strain (B13117), consistent with preferential diversion of hexose-6-phosphate to polysaccharide in B13117. We conclude that while the ED pathway is rare amongst Campylobacter isolates causing human disease (the majority of which would be of agricultural origin), some glucose-utilizing isolates exhibit specific fitness advantages, including stationary-phase survival and biofilm production, highlighting key physiological benefits of this pathway in addition to energy conservation.

Analyses of energy metabolism and stress defence provide insights into Campylobacter concisus growth and pathogenicity

“…Furthermore, C. concisus does not have genes for the ED pathway or for fucose catabolism, unlike as documented in certain C. jejuni strains ( Fig. 1 and Additional file 1: Table S1 and Additional file 5: Table S5) [38]. Collectively, these findings support the previous characterization of C. concisus as non-saccharolytic [1].…”

“…doylei 269.97 (NC_009707.1) and not found in most C. jejuni subsp. jejuni strains [38]. In addition, the tetrathionate reductase genes tsdA (C8J_0815) and the tsdA paralog (C8J_0040) were discovered in C. jejuni strain 81116 [50].…”

“…jejuni has a highly branched electron transport chain, with a range of electron transport routes available, and the ability to use diverse substrates as electron donors [25,34]. This includes organic acids such as formate [35,36], gluconate [37,38], lactate [39], and in particular the TCA cycle intermediates pyruvate [40], 2-oxoglutarate [41], succinate [42], fumarate [42] and malate [36]. Hydrogen gas (H 2 ) [35,43] and sulphite [44] can also be used as electron donors.…”

Characterisation of Aerotolerant Forms of a Robust Chicken Colonizing Campylobacter coli

“…However, the adaptation present in the aerotolerant C. coli OR 12 also enables aerobic growth on CCDA. Modifications to central metabolism are emerging amongst campylobacters, for example it was recently reported that 1.7% of thermophilic campylobacters have the potential to metabolize glucose via the Entner-Doudoroff pathway (Vegge et al, 2016). This pathway also permits the metabolism of L -fucose, which has been reported to provide a competitive advantage to C. jejuni in a piglet colonization model (Stahl et al, 2011).…”

Enzymatic Synthesis of 2-Keto-3-Deoxy-6-Phosphogluconate by the 6-Phosphogluconate-Dehydratase From Caulobacter crescentus

“…2-keto-3-deoxy-6-phosphogluconate (KDPG) is the key metabolite of the Entner-Doudoroff (ED) pathway -also known as the KDPG pathway -which is estimated to be utilized by 27% of the heterotrophic prokaryotic microorganisms for sugar and sugar acid (e.g., gluconate) degradation and has recently been found to play also a significant role in cyanobacteria, algae and even higher plants (Flamholz et al, 2013;Chen et al, 2016). Among the ED pathway utilizing organisms there are numerous human pathogens like Escherichia coli, Salmonella enterica, Neisseria gonorrhoeae, Klebsiella pneumoniae, Helicobacter pylori, Pseudomonas aeruginosa, Legionella pneumophila, Campylobacter spp., and Pasteurella pestis (Patra et al, 2012;Vegge et al, 2016;Gonzalez-Mula et al, 2019). In addition, several plant pathogens like Xanthomonas campestris, Pectobacterium carotovorum, Agrobacterium tumefaciens and other organisms of agricultural importance, like Rhizobiaceae, as well as some organisms of biotechnological interest like e.g., Zymomonas mobilis, Gluconobacter oxydans, are ED pathway utilizers (Stowers, 1985;Richhardt et al, 2012;He et al, 2014).…”