In this study, we investigated the question of the impact of glyphosate formulation on Salmonella enterica isolates in context of animal health and environmental hygiene. Within a screening of 225 S. enterica isolates from farm animals, a change in susceptibility within the last three decades became visible. Different susceptibility against glyphosate was found between different serovars and host animals. In general, the screening revealed higher MIC in isolates that were isolated in the last years. Also, higher MICs were found in pigs compared to poultry and cattle and the serovar Typhimurium had a higher MIC compared to Enteritidis and Infantis. This was the case not only for glyphosate as a pure substance but also for the formulation Roundup LB plus. In an in vitro fermenter experiment, we investigated whether this generally higher glyphosate tolerance in S. enterica lead to a better survival within cattle intestine e.g. rumen. Therefore, we performed an experiment with rumen simulation technic and infected fermenter vessels with S. enterica. Afterwards we challenged half of the vessels with RU, re-isolated S. enterica, counted them and determined the MIC to RU of the re-isolates. It turned out, that RU had no impact on survival time of S. enterica in fermenter, that no change of MIC within experiment took place and that no cross-resistance to antibiotics occurred. In laboratory experiments we finally investigated if it is possible to generate glyphosate resistance in S. enterica via a long-term evolution experiment. We challenged the pathogen with sub-lethal concentrations of RU. It was not easy to decrease sensitivity in S. enterica isolates and many days were needed. In the end, three isolates were selected due to a two to four times higher MIC after the experiment. Of these isolates, the whole genome was sequenced. Comparisons with sequenced ancestral strains revealed mutations in the aroA gene and close regions, but also revealed mutations in genes for stress response. In a fitness essay, no fitness costs were measurable. Also, no cross-resistance or cross-tolerance to antibiotics could be detected. In comparison of the proteome of ancestor and mutant not only the increase of EPSPS translation was visible, but also a variety of different proteins were up- and down-regulated, linked with stress response, iron metabolism and reproductions. In an in vivo animal trial, we finally wanted to investigate the impact of glyphosate and GBH on the shedding of S. enterica. Therefore, three groups of weaning piglets were fed with RU or glyphosate or functioned as control group. In qualitative analysis a significantly higher number of S. enterica was only found in colon samples of the control group compared to the RU group. All other comparisons, qualitatively and quantitatively, showed no differences between the control group, the group fed with glyphosate or the group fed with RU. The findings show a relatively low impact of glyphosate and glyphosate based herbicides in complex environments and with worst-case but still realistic concentrations on the survival, selection and shedding of S. enterica. In laboratory surroundings, it was possible to generate glyphosate resistant S. enterica isolates. These isolates showed mutations in the aroA gene. Furthermore, there was an inconsistent picture of the changes in adaptation to RU which can be brought back to other effects of glyphosate, apart from target enzyme and the effects of the undeclared ingredients of glyphosate formulation.
