1 November 2021

A first pilot study provides the basis for further extended analyses

There was great joy last year when an interdisciplinary research consortium from Basel led by the Biozentrum (Prof. C. Dehio, Prof. D. Bumann, Prof. U. Jenal) received the Swiss National Science Foundation (SNSF) National Centre of Competence in Research (NCCR) award for their project "AntiResist" (we reported here). AntiResist aims to develop new strategies to combat antibiotic-resistant bacteria within the funding period of 12 years. Prof. Nina Khanna's research group at the University Hospital Basel (USB) is a clinical partner within AntiResist and, with the support of the Department of Clinical Research, is now providing initial findings from investigations of tissue samples from infected patients.

Until now, antibiotics research has involved cultivating pathogenic bacteria in the laboratory and then studying them - under optimal but artificial conditions. New technical developments make it possible to study bacteria in their natural environment, i.e. directly in infected human tissue. In the case of AntiResist, this comes from patients from the USB who are being treated for an infection. The approach is now from "patient to drug" instead of the traditional "drug to patient".

This approach was tested in the PROSA study, which has now been completed (see right). As a pilot study, it provided important empirical values for establishing the procedures and requirements for data acquisition, data transfer and data evaluation of the tissue samples analysed for Staphylococcus aureus. The new research approach poses a number of challenges and requires innovative data solutions.


Richard Kühl

The experience gained from the PROSA study has enabled us to optimise data acquisition on the bacterium Staphylococcus aureus when measuring directly in patient material.

Dr. Richard Kühl, DKF research group of Prof. Nina Khanna

In recent months, the research group's collaboration with the USB Clinical Data Warehouse, the Biozentrum, and the DKF has made great progress in the collection and development of the complex data structure and data infrastructure. All this experience is now being brought into the NCCR AntiResist project, with the aim of studying additional bacteria and linking them to clinical outcomes. Specifically, the PROSA study is currently being expanded to include other pathogens: E. coli, P. aeruginosa and K. aerogenes .

In the long term, it is AntiResist's goal to develop new therapy options on the basis of all these data and to investigate them in clinical trials.

Antiresist
PROSA Study

"PRoteomics Of Staphylococcus Aureus"

Principal Investigators

Prof. Nina Khanna, Senior Physician, Co-Head of Consultation Service, USB, and research group leader at the Department of Biomedicine (DBM) and DKF (Project Leader)

Dr. Richard Kühl, Senior Physician Clinic for Infectiology & Hospital Hygiene at the USB and member of the DBM/DKF research group of Prof. Nina Khanna (Deputy Project Leader)

Study design

Monocentric, prospective observational study

Project duration

2017-2020

Aim

To improve the understanding of the relationship between antibiotic therapy, resistance development and adjustment of virulence factors in patients infected with Staphylococcus aureus.

Procedure

Patients undergoing surgical procedures in hospital and diagnosed with Staphylococcus aureus infection may be included in the study. Samples will be taken from the site of infection during the procedure. In addition, blood from routine samples will be used for further analysis.

Analyses

  • High sensitivity mass spectrometry with whole genome sequencing to analyze both virulence factor expression and genomic alterations of Staphylococcus aureus in tissue.
  • Antibiotic concentrations in tissue and blood using chromatographic methods.

Funding

NCCR AntiResist

Supported by DKF through

Data Management, Data Analysis/Statistics, Regulatory Affairs