Completed project: Pathways of antibiotic resistance uncovered

Multidrug-resistant pathogens spread in various ways. Among other things, they pass from animals hospitalied in veterinary clinics to humans and are introduced unnoticed by travellers. Thanks to the new genome sequencing methods, scientists at the University of Bern have been able to demonstrate this in detail for the first time.

In recent years, many multidrug-resistant bacteria have become widespread. This is particularly true for the Gram-negative pathogens such as Escherichia coli, Klebsiella spp. and Salmonella spp., whose infections are difficult to treat. As new resistance variants are constantly emerging, it is important to quickly identify their origin, routes of spread and genetic characteristics. This enables both targeted intervention in outbreaks and preventive measures.

However, antibiotic resistance spreads via a variety of pathways, including the transfer of mobile genetic elements that can be exchanged between different bacterial species. This capacity plays a major role in the transmission of antibiotic resistance among animals, humans and the environment. This phenomenon mostly occurs silently, as does the unnoticed gut colonisation of humans with antibiotic-resistant bacteria, without necessarily leading to outbreaks. Therefore, until recently it has hardly been possible to uncover such transmission pathways in detail because adequate methods to do so were lacking.

Thanks to the advent of the new genome sequencing technologies, bacteria can now be quickly and comprehensively analysed. In fact, the whole-genome sequencing provides information regarding both chromosome and mobile genetic elements. This allows bacterial strains to be compared with each other and conclusions to be drawn about how closely related the pathogens are or whether resistance is related. Andrea Endimiani and a team of researchers from the Institute of Infectious Diseases (IFIK) and the Institute of Veterinary Bacteriology Bern (IVB) have thus sequenced over 1600 samples of multidrug-resistant enterobacteria. The samples came from patients, foodstuffs, farmed animals, wild animals and wastewater. By linking the data obtained with each other and with epidemiological data on the patients concerned, the researchers obtained information on how certain resistances spread across humans, animals, the food chain and environmental domains.

Among other things, they found multidrug-resistant Escherichia coli bacteria in two stool samples from employees of veterinary clinics which were clearly identical to strains that they had previously detected in dogs and cats at these clinics. Furthermore, they discovered high-risk clones of highly-resistant Klebsiella pneumoniae in the immediate vicinity of a veterinary clinic. The genetic analysis also revealed that these strains were identical to those causing infections in pets hospitalised at the clinic. These results suggest that the infection control procedures already implemented in the human clinics should also be implemented in the veterinary clinics. In addition, in the interests of early outbreak detection, it would be important to report to the Federal Institutions the detection of certain resistant pathogens (e.g., those producing carbapenemases) in companion animals, as is already the case in human medicine.

In another study, the researchers collected stool samples from 37 Zanzibar travellers, each before departure and after return. The Escherichia coli strains isolated from the stools were compared to those found on people in Zanzibar and on locally retailed chicken meat and other poultry. It was found that at least one-third of the travellers were newly colonised with resistant strains clearly originating from Zanzibar upon return. The researchers conclude that travellers returning from countries with a high prevalence of multidrug-resistant pathogens often introduce such new bacteria. However, as they usually do not show any signs of illness, but are merely colonised by the pathogens, appropriate screening measures should be considered. The researchers also recommend developing new strategies for the decolonisation of the intestinal tract.

The project not only revealed important transmission pathways of individual antimicrobial resistances, but also fundamentally demonstrated the enormous potential of the new whole-genome sequencing methods. These analyses are just as suitable for quickly tracing the routes of spread of resistant pathogens in local outbreaks as they are for constantly monitoring the national and global spread of multidrug-resistant "superbugs".

September 2021