Background
Antibiotic resistance is an increasing worldwide problem that complicates medical procedures, including surgeries and cancer treatments, increases costs for treatment of infections and threatens safe food production. The world health organization and the United Nations have recognized antibiotic resistance as one of the greatest threats to human welfare. It has been recognized that a One Health approach is required to solve the problem. This means that the human (medical), animal (veterinary), and environmental sectors all have to work together to stop spread of antibiotic resistance that ultimately can affect human health.
All over the world, ionophores are used as feed additives in animal husbandry. Ionophores are antibiotic compounds that are active against bacteria, fungi, viruses, and parasites. They are used extensively in poultry production to prevent coccidiosis (an intestinal parasite disease that have severe economical consequences to the meat industry) and to alter the ruminant microbiota of cattle to increase feed conversion. Ionophores are not used in human medicine and have for a long time been considered safe for use, from an antibiotic resistance perspective. However, an ionophore resistance mechanism was recently discovered and it was shown that it is physically linked (located on the same plasmid) to a vancomycin resistance mechanism in the human opportunistic pathogen Enterococcus faecium. This can explain the persistence of Vancomycin resistant Enterococcus faecium (VRE) in Norwegian and other countries poultry populations even though vancomycin has never been used and an analogous compound (avoparcin) was banned from use almost 30 years ago. VRE are among the highest ranked pathogens on the WHO list of pathogens in critical need of research and development of new preventive and treatment measures. Persistence of VRE in animal populations could increase the risk of spread to humans via food products or direct contact with animals or the animal environment.
Goal
This project aims at determining the ability of enterococci to tolerate and become resistant to ionophores and to understand how the underlying ionophore resistance mechanisms works.
Project plan
We will perform basic microbiology experiments to isolate adapted or mutated bacteria that are more tolerant or resistant to ionophores. Eventual mutants will be whole genome sequenced in order to identify the mutation. The mutated genes will be cloned and characterized by mutational analyses in an Enterococcus spp. Host and potentially by purification and characterization in vitro. Eventual adapted (more tolerant strains) will be compared to non-adapted strains in fitness assays, and by RNA sequencing and/or proteomics analyses to identify potentially upregulated genes giving rise to the increased tolerance. Pilot experiments have shown that enterococci can adapt to growth in the presence of ionophores, which is promising for further characterization of the mechanism of action.
The research group
The research group is young and dynamic and currently consists of 5 people located at UiO. The project is part of a large collaborative project funded by the Joint Program Initiative for Antimicrobial Resistance and the Research Council of Norway with participants from Norway, the Netherlands, Poland, Italy and France.