Our research explores two interconnected topics: 1. Infectious disease diagnostics using metabolomics for rapid identification of causative bacteria and antibiotic resistance traits. 2. Infectious disease epidemiology using microbial genotyping and spatial models
We have recently commenced metabolomic studies of specimens from humans with severe sepsis and from laboratory mice with experimental infection aiming at early specific detection of bacterial infections and identification of biomarkers for disease severity. The work is collaboration between researchers from the fields of molecular biology, chemistry, bioinformatics and clinicians in infectious diseases.
The figure above shows a multivariate analysis of metabolites in blood samples of humans with severe sepsis. Six patients infected with S. aureus were compared with 10 patients with E. coli. The two infections could easily be distinguished by analysing the metabolome at admission to the Intensive Care Unit. After the start of antibiotic treatment there was a convergence of the metabolomic profiles with time.
High-resolution genotyping is used in our research for studying transmission routes of bacteria and their acquisition of various resistance genes in hospitals, the society, and reservoirs in nature. We are using clinical specimens for doing molecular epidemiology and population genetic studies of infections caused by Escherichia coli, Staphylococcus epidermidis, and Francisella tularensis.
An example analysis is provided in the figure to the left.
548 E. coli isolated from humans with urinary tract infection were characterized by sequencing of 7 gene fragments. The genetic relationship among the bacteria is shown as dots with dot sizes proportional to the number of isolates.
The different colors indicate different variants of resistance genes encoding trimethoprim resistance.
By means of large scale whole genome sequencing of F. tularensis that is causing the disease tularemia, we are tracking the spread of the disease to humans from its sources in nature. Tularemia is a rare disease worldwide making the experience with outbreak investigations very limited. Sweden and the MIMS-environment in particular, however provide excellent opportunities for such investigations. Large outbreaks occur regularly among humans in Sweden. By cooperation with physicians F. tularensis can be isolated from many patients with tularemia. Each isolate can be genome sequenced and correlations made with detailed epidemiological data for finding sources of infection.