Practical applications of whole genome sequencing for reservoir epidemiology, molecular surveillance, and antimicrobial susceptibility testing of extended-spectrum ß-lactamase producing Escherichia coli

Abstract

The World Health Organization declared antimicrobial resistance (AMR) one of the top 10 public health threats facing humanity. In Europe, ESBL-producing Escherichia coli (ESBL-Ec) is the most important cause of AMR infections. The studies in this thesis provided information on how practical applications of a technique, whole genome sequencing (WGS), can increase resilience against ESBL-Ec. WGS is used to decode and digitalise the genetic code of organisms, and in this case of the bacterium ESBL-Ec. Most important findings: -The probability of an E. coli to carry AMR is determined by its genetic ‘backbone’. Certain variants are responsible for a disproportionate burden of disease of AMR and might be of interest for directed infection prevention or vaccine development. -A person’s own ESBL-Ec carriage in the gut is likely the most important source of an infection with ESBL-Ec. -In Europe, human carriage is mostly caused by transmission from another human being. Non-human sources like food are likely less common. -We found some evidence for transfer of genetic material encoding antimicrobial resistance between ESBL-Ec and another species: Klebsiella pneumoniae. More research is needed to determine how this type of transfer is within the problem of AMR. -ESBL-Ec detected in urine- and blood-cultures collected from routine clinical care give a representative view of the genetic variants of ESBL-Ec circulating in the Dutch community. Thus, clinical cultures are suitable for genetic surveillance of ESBL-Ec in the Dutch community. -We tested two available tools to predict antimicrobial resistance in E. coli infections. Both did not meet the quality-criteria of the U.S. Food and Drug Administration for new antimicrobial susceptibility tests