{"type": "FeatureCollection", "features": [{"id": "10.1101/2024.01.17.575993", "type": "Feature", "geometry": null, "properties": {"updated": "2026-07-27T16:19:12Z", "type": "Journal Article", "created": "2024-01-19", "title": "Exposure of gut bacterial isolates to the anthelminthic drugs, ivermectin and moxidectin, leads to antibiotic-like phenotypes of growth inhibition and adaptation", "description": "Abstract

Due to their broad-spectrum activities, ivermectin and moxidectin are widely used anthelminthics in veterinary and human medicine. However, ivermectin has recently been shown to perturbate gut-microbial growth. Given the macrolide-like structure of both ivermectin and moxidectin, there is a need to characterize the antibiotic spectrum of these anthelminthic drugs and their potential implications in the development of cross-resistance to macrolides and other families of antibiotics. Here, we incubated 59 bacterial isolates representing different clades frequently found in the gut with ivermectin and moxidectin at different concentrations for 16-72h. Further, we challenged 10 bacterial isolates with repeated and gradually increasing concentrations of these two anthelminthics and subsequently characterized their sensitivity to different antibiotics as well as ascending anthelminthic concentrations. We found, that antibacterial activity of the two anthelminthics is comparable to a selection of tested antibiotics, as observed by potency and dose dependence. Bacterial anthelminthic challengingin vitroresulted in decreased anthelminthic sensitivity. Further, adaptation to anthelminthics is associated with decreased antibiotic sensitivity towards three macrolides, a lincosamide, a fluoroquinolone, a tetracycline and two carbapenems. The observed change in bacterial sensitivity profiles is associated with - and likely caused by - repeated anthelminthic exposure. Hence, current and future large-scale administration of ivermectin and moxidectin, respectively, for the control of helminths and malaria raises serious concerns - and hence potential off-target effects should be carefully monitored.Ammonia\uffe2\uff80\uff90oxidising archaea (AOA) are important microorganisms contributing towards the nitrogen flux in the environment. Unlike archaea from other major phyla, genetic tools are yet to be developed for the AOA, and identification of antibiotic resistance markers for selecting mutants is required for a genetic system. The aim of this study was to test the effects of selected antibiotics (hygromycin B, neomycin, apramycin, puromycin, novobiocin) on pure cultures of three well studied AOA strains, \uffe2\uff80\uff98Candidatus Nitrosocosmicus franklandianus C13\uffe2\uff80\uff99, Nitrososphaera viennensis EN76 and Nitrosopumilus maritimus SCM1. Puromycin, hygromycin B and neomycin inhibited some but not all tested archaeal strains. All strains were resistant to apramycin and inhibited by novobiocin to various degrees. As N. viennensis EN76 was relatively more resistant to the tested antibiotics, a wider range of concentrations and compounds (chloramphenicol, trimethoprim, statins) was tested against this strain. N. viennensis EN76 was inhibited by trimethoprim, but not by chloramphenicol, and growth recovered within days in the presence of simvastatin, suggesting either degradation of, or spontaneous resistance against, this compound. This study highlights the physiological differences between different genera of AOA and has identified new candidate antibiotics for selective enrichment and the development of selectable markers for genetic systems in AOA.Due to their broad-spectrum activities, ivermectin and moxidectin are widely used anthelminthics in veterinary and human medicine. However, ivermectin has recently been shown to perturbate gut-microbial growth. Given the macrolide-like structure of both ivermectin and moxidectin, there is a need to characterize the antibiotic spectrum of these anthelminthic drugs and their potential implications in the development of cross-resistance to macrolides and other families of antibiotics. Here, we incubated 59 bacterial isolates representing different clades frequently found in the gut with ivermectin and moxidectin at different concentrations for 16-72h. Further, we challenged 10 bacterial isolates with repeated and gradually increasing concentrations of these two anthelminthics and subsequently characterized their sensitivity to different antibiotics as well as ascending anthelminthic concentrations. We found, that antibacterial activity of the two anthelminthics is comparable to a selection of tested antibiotics, as observed by potency and dose dependence. Bacterial anthelminthic challengingin vitroresulted in decreased anthelminthic sensitivity. Further, adaptation to anthelminthics is associated with decreased antibiotic sensitivity towards three macrolides, a lincosamide, a fluoroquinolone, a tetracycline and two carbapenems. The observed change in bacterial sensitivity profiles is associated with - and likely caused by - repeated anthelminthic exposure. Hence, current and future large-scale administration of ivermectin and moxidectin, respectively, for the control of helminths and malaria raises serious concerns - and hence potential off-target effects should be carefully monitored. Ammonia\uffe2\uff80\uff90oxidising archaea (AOA) are important microorganisms contributing towards the nitrogen flux in the environment. Unlike archaea from other major phyla, genetic tools are yet to be developed for the AOA, and identification of antibiotic resistance markers for selecting mutants is required for a genetic system. The aim of this study was to test the effects of selected antibiotics (hygromycin B, neomycin, apramycin, puromycin, novobiocin) on pure cultures of three well studied AOA strains, \uffe2\uff80\uff98 Candidatus Nitrosocosmicus franklandianus C13\uffe2\uff80\uff99, Nitrososphaera viennensis EN76 and Nitrosopumilus maritimus SCM1. Puromycin, hygromycin B and neomycin inhibited some but not all tested archaeal strains. All strains were resistant to apramycin and inhibited by novobiocin to various degrees. As N. viennensis EN76 was relatively more resistant to the tested antibiotics, a wider range of concentrations and compounds (chloramphenicol, trimethoprim, statins) was tested against this strain. N. viennensis EN76 was inhibited by trimethoprim, but not by chloramphenicol, and growth recovered within days in the presence of simvastatin, suggesting either degradation of, or spontaneous resistance against, this compound. This study highlights the physiological differences between different genera of AOA and has identified new candidate antibiotics for selective enrichment and the development of selectable markers for genetic systems in AOA.