Metabolomics, an analytical study with high-throughput profiling, helps to understand interactions within a biological system.Small molecules, called metabolites or metabolomes with the size of <1500Da, depict the status of a...

Metabolomic reprogramming plays a crucial role in the activation of several regulatory mechanisms including neuronal responses of the host. In the present study, alterations at physiological and biochemical levels were initially assessed to monitor the impact of the candidate pathogen Cronobacter sakazakii on the nematode host Caenorhabditis elegans. The abnormal behavioral responses were observed in infected worms in terms of hyperosmolarity and high viscous chemicals. The microscopic observations indicated reduction in egg laying and internal hatching of larvae in the host. An increased level of total reactive oxygen species and reduction in antioxidant agents such as glutathione and catalase were observed. These observations suggested the severe effect of C. sakazakii infection on C. elegans. To understand the small molecules which likely mediated neurotransmission, the whole metabolome of C. elegans during the infection of C. sakazakii was analyzed using liquid chromatography−mass spectrometry. A decrease in the quantity of methyl dopamine and palmitoyl dopamine and an increase in hydroxyl dopamine suggested that reduction in dopamine reuptake and dopamine neuronal stress. The disordered dopaminergic transmission during infection was confirmed using transgenic C. elegans by microscopic observation of Dat-1 protein expression. In addition, reduction in arachidonic acid and short-chain fatty acids revealed their effect on lipid droplet formation as well as neuronal damage. An increase in the quantity of stearoyl CoA underpinned the higher accumulation of lipid droplets in the host. On the other hand, an increased level of metabolites such as palmitoyl serotonin, citalopram N-oxide, and N-acyl palmitoyl serotonin revealed serotonin-mediated potential response for neuroprotection, cytotoxicity, and cellular damage. Based on the metabolomic data, the genes correspond to small molecules involved in biosynthesis and transportation of candidate neurotransmitters were validated through relative gene expression.

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Cronobacter sakazakii , an opportunistic foodborne pathogen prevalently detected in contaminated powdered infant formula, is associated with different diseases, including meningitis. It can cross the blood-brain barrier and affects the CNS.

Background: Bacterial effector molecules are the crucial infectious agents and are su cient to cause pathogenesis. In the present study, pathogenesis of Salmonella enteric serovar Typhi (S. Typhi) toxic proteins on the model host Caenorhabditis elegans was investigated by exploring the host regulatory proteins during infection through quantitative proteomics approach. In this regard, the host protein extract was analysed using two-dimensional gel electrophoresis (2D-GE) and differentially regulated proteins were identi ed using MALDI TOF/TOF/MS analysis.Results: Out of the 150 regulated proteins identi ed, 95 proteins were appeared to be downregulated while 55 were upregulated. Interaction network for regulated proteins was predicted using STRING tool. Most of the downregulated proteins were found to be involved in muscle contraction, locomotion, energy hydrolysis, lipid synthesis, serine/threonine kinase activity, oxidoreductase activity and protein unfolding and upregulated proteins were found to be involved in oxidative stress pathways. Hence, cellular stress generated by S. Typhi protein extract on the model host was determined using lipid peroxidation, oxidant and antioxidant assays. In addition to that the candidate proteins resulted from the host protein extract analysis were validated by Western blotting and roles of several crucial molecular players were analyzed in vivo using wild type and mutant C. elegans.Conclusions: To the best of our knowledge, this is the rst study to report the protein regulation in host C. elegans during S. Typhi toxic proteins exposure which highlights the signi cance of p38 MAPK and JNK immune pathways.

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