FEAR - Frequency of environmental antibiotic resistance

Several genetically modified organisms (=GMOs) currently under risk evaluation by EFSA contain nptII or nptIII as antibiotic resistance marker (=ARM) genes. Both aminoglycoside phosphotransferases inactivate a bulk of aminoglycoside antibiotics (nptII: kanamycin, neomycin, paromomycin, ribostamycin, butirosin, gentamicin B, geneticin; nptIII: additionally amikacin and isepamicin), some of them crucial and/or second line antimicrobials. Horizontal transfer of intact ARM genes from plants to prokaryotes has been observed only under optimized laboratory conditions, yet. However, ARM gene transfer from plant to bacteria in natural habitats cannot be excluded entirely, introducing an option for interference with animal and human antimicrobial chemotherapy. Facing the current global crisis in the treatment of infectious diseases a preservation of all therapeutic options is mandatory and warrants a closer look on quantitative aspects of the prevalence of nptII and nptIII in naturally occurring bacterial populations (i.e. background resistance rates). The determination of this “baseline” will provide the reference for assessing the effects of artificially introduced ARM genes in a quantitative manner. The impact of laterally transferred ARM gene fragments has not been in the research focus, yet. A quantitative approach (i.e. the determination of the number of introduced and endogenously present corresponding resistance determinants) is necessary to eliminate uncertainties and should help to improve the risk assessment of plant gene derived ARM genes. The proposed project aims at the following: 1. Acquisition of the baseline prevalence of nptII and nptIII in the microbial gene pool of representative naturally occurring bacterial populations in Austria. 2. Documentation of the occurring selection pressure by monitoring the application of antibiotics in selected Austrian habitats (Monitoring program “Antibiotikamengenströme in Österreich”) and determination of antibiotic concentrations in selected habitats. 3. Development of a computer model simulating the effects of artificially introduced resistance determinants in various bacterial populations. 4. Determination of environmental conditions supportive for the formation of aminoglycoside phosphotransferases with mosaic gene structures. Two operational AGES research units (DSR, Human Medicine) will perform the tasks working in close collaboration with the University of Applied Life Sciences (Department of Integrative Biology and Biodiversity Research) and the University of Tromsö (Department of Pharmacy).