Host and pathogen biomarkers to predict bacterial sepsis

Sepsis is defined as life threatening organ dysfunction caused by a dysregulated host response to infection, and is responsible for 52,000 deaths in the UK per year. Approximately 50% of sepsis episodes are related to bacteria where the Gram-negative bacteria Escherichia coli is a leading causative agent. Our previous work with the Hywel Dda Health Board has identified a high level of E. coli sepsis and in the current work, we aim to identify genetic (genes) and host biomarkers (e.g. IL-6) to discriminate E. coli sepsis isolates based on original source of infection.

E. coli isolates (n=100) from blood cultures in patients with defined sources of infection (urinary, biliary, intra-abdominal or unknown) were used to investigate potential biomarkers using next generation sequencing, whole blood modelling and molecular microbiology phenotyping.

Sequencing of isolates is underway. Growth curve analysis demonstrated that human serum could modulate E. coli growth to three phenotype groups; i) no growth, ii) retarded / decreased growth and iii) unaffected growth (compared to LB control). Whole blood modelling over 6 hours confirmed 4 hours to be the optimal time point to study IL-6 expression. Grouping isolates by source of infection showed that those from the urinary tract and ‘unknown’ sources produced significantly more IL-6 than E. coli K12. Completion of phenotyping will allow association studies to bacterial genotype.

These results will help define new biomarkers associated with the host and genetic biomarkers associated with E. coli that will better predict and inform the diagnosis and treatment of sepsis.