Full length articleGlucose enhances tilapia against Edwardsiella tarda infection through metabolome reprogramming
Introduction
Edwardsiella tarda is a type of Gram-negative pathogen that belongs to the Enterobacteriaceae family [1]. E. tarda infects both human and fish, thus raising public concerns and causing huge economic loss in aquaculture, respectively, throughout the world. Elucidation of the mechanism underlying E. tarda pathogenesis becomes urgent in current years. Although studies have been performed via genomics, proteomics and transcriptomics to address the molecular steps of bacteria invasion into host cells, none effective way had yet been proposed to control infections [1], [2], [3], [4], [5].
Although antibiotics are always the preferable choices to manage bacterial infection both in hospital and in fish farming, the emergence of antibiotic-resistant bacteria strains is the severe consequence of the overuse or misuse of antibiotics [6]. The development of antibiotic-resistant bacteria creates the potential for epidemics of infection that are either untreatable or which can be only treated by one or a few antibiotics. This thus brings higher degree of threat to human beings. Vaccination with live bacteria or inactivated bacteria is an alternative approach to prevent infections [5], [7]. It has high protection efficiencies and does not much side effects as other methods. However, the development of effective vaccines is time- and labor-cost, and now no commercial vaccine is available for control of this bacterium. Therefore, boosting the host's immune response is a more ideal approach.
Reprogramming metabolomics is a recently proposed approach to revert host's phenotype through exogenous administration of metabolites [8]. Independent researches from our group and other groups showed the exogenous metabolites like glucose, fructose or alanine could potentially revert the kanamycin-resistant bacteria to kanamycin-sensitive bacteria [9], [10]. The phenotype shift was highly dependent on the exogenous metabolites to reprogram metabolome from current status to a new status that favors the uptake of extracellular antibiotics like kanamycin. This reprogram capability of exogenous metabolites was not only observed in bacteria. Using similar approach, we have demonstrated that unsaturated linoleic acid, glucose, N-acetylglucosamine, l-leucine, and myo-inositol potentiate host's ability to clear pathogens like E. tarda, Streptococcus agalactiae, balofloxacin-resistant bacteria, and Streptococcus iniae [11], [12], [13]. Moreover, exogenous glycine and serine would increase the growth and antifungus activity of a newly isolated strain from Southwest Indian Ocean, showing a broad application of reprogramming metabolomics [14].
Recently, we have shown that the infection of E. tarda to tilapias would suppress the glucose level in fish liver [15]. However, the exogenous glucose to the fish would greatly enhance their survival ability. This mechanism of the potentiation was not explored yet. Here, we performed in-depth investigation of how glucose would enhance fish survival after bacteria challenge. And we found that the exogenous glucose was preferably converted into fatty acid, which could replace glucose as important source to help fish fight against pathogens.
Section snippets
Bacteria strains and fish
E. tarda EIB202 (CCTCC M208068) used in the present study was kindly provided by Professor YX Zhang, East China University of Science and Technology, China. Bacteria were grown in 100 mL tryptic soy broth (TSB) medium at 30 °C overnight and then diluted 1:100 into fresh TSB medium until its absorbance value of OD600 equal to 1.0.
Juvenile nile tilapias(body length: 6 ± 0.5 cm, body weight: 2.5 ± 0.2 g), Orechromis niloticus, purchased from a tilapia breeding Corporation (Guangzhou, P.R. China)
Metabolic profiles of Oreochromis niloticus injected with glucose
Exogenous glucose protects fish from Edwardsilla tarda EIB202 infection, and decreased fish mortality from 30% to 60% as previous described (Fig. 1A) [15]. To explore the underlying mechanism of glucose protection efficacy, we adopt functional metabolomics to investigate how exogenous glucose modulates fish's metabolome for such protection. We investigate metabolic profiles in response to glucose addition as outline in Fig. 1B. Livers were obtained from fish injected with either saline
Discussion
We recently proposed that crucial metabolite biomarkers identified through metabolome analysis could modulate the metabolic status of hosts, thereby shift their phenotype from one to another, named as reprogramming metabolomics[9]. This metabolic intervention approach circumvents problems imposed by conventional methods like antibiotics or vaccines, in fighting with bacterial infections in fish. The key to this approach was based on the metabolites or metabolic pathways that has been disrupted
Conflict of interests
All the authors declared no conflict of interests.
Acknowledgement
This work was sponsored by grants from Science and Technology Program of Guangzhou (201504010025), key project of Natural Science foundation of Guangdong (2015A030308009), NSFC projects (41276145, 31572654, 31672656),National research and development key project(2016YFD0501307).
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