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Ashok Kumar, Pawan Kumar Singh, Shailendra Giri; Metabolic signatures of Staphylococcus aureus endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5871. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Microbial infections are known to perturb host metabolism, yet metabolic alterations in bacterial endophthalmitis have not been investigated. In this study, we performed the global metabolomics on S. aureus-infected mouse retina to investigate the metabolic changes that occur during various stages of endophthalmitis.
Endophthalmitis was induced in C57BL/6 mice via intravitreal injections of S. aureus (5000 cfu/eye). At various time-point (6, 12, 24, 48, and 72h; n = 18/time point) post-infection, neuroretina (without RPE and choroid) were removed and froze immediately. PBS injected eyes/retina served as uninfected controls. Retinal tissue was subjected to global untargeted metabolomics utilizing ultra-high-performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy.
Metabolomics analysis identified a total of 510 metabolites that belonged to the lipid (35%), amino acid (28%), nucleotide (11%), carbohydrate (7%), peptide (5%), xenobiotic (5), and energy (2%) pathways. Metabolite changes were detected as early as 12h post infection, well before the retinal function loss and tissue destruction, which testifies to the sensitivity of this methodology. S. aureus infection led to significant alterations in metabolites and pathways related to inflammation (fatty acids, eicosanoids and histamine) and energy-metabolism (glucose, TCA cycle, glycogen, acylcarnitines, branched-chain amino acid catabolites). Changes related to oxidative stress, arginine metabolism, and nucleotide metabolism were also observed in the S. aureus-infected retina in a temporal manner. A significant induction of metabolites of polyunsaturated fatty acids (PUFA), specifically the alpha-linolenic acid upon infection might be associated with resolution of inflammation.
Our study provides a comprehensive metabolic profile of staphylococcal endophthalmitis. Insights from this study provide opportunities for developing new diagnostic markers and novel approaches for treatment or prevention of endophthalmitis, where targeting metabolism might be a new avenue of therapy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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