Identifying host and bacterial biomarkers to predict sepsis
End of project summary
Main messages
Sepsis is a medical emergency, requiring immediate administration of supportive therapy and antibiotics. Therefore, identifying markers that predict the patients that might succumb to sepsis is vital. This project has worked with the Hywel Dda University Health Board (HDUHB) to study a sub-group of the E. coli bacteria that causes sepsis. This project has established a collection of these bacteria and identified important markers (genes) that allow them to reach and survive in the bloodstream. These markers define the immune responses (cytokines) generated and will form the basis of future tests to predict sepsis.
Result highlights
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105 sequenced isolates from HDUHB were characterised for their genetic elements, families and sequence types-77% belong to phylogroup B2, and 21%, 19% and 9% belong to ST131, ST73 and ST12 respectively
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Isolates had linked patient data associated with origin of infection, sepsis incidence and nosocomial infection incidence
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Immune responses in our laboratory model showed increased IL-8 and MIP- 3α in bacteraemia isolates versus control isolates
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Immune responses in our laboratory model showed that Serum resistant isolates induce more IL-6, IL-8 and resist in than serum sensitive isolates
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Immune responses in our laboratory model showed that abdominal isolates induced more IL-8 and MIP3α than water isolate controls
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papG, papC, sfaC, kpsM, chuA, iucC, iucD and iroB are found at a higher incidence in the bacteramia strains than across the whole E. coli species
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sfaX is found at a higher incidence in urinary than abdominal isolates
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sfaC is found at a higher incidence in abdominal than urinary isolates
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Genes associated with clinical phenotypes; yhgE, ybjE, tufB and yohF
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Association with laboratory phenotypes; ynbC, and yejF
The project has identified numerous host and bacterial specific biomarkers as candidates for early diagnosis of bacteraemia and sepsis