TY - CONF A1 - Schreiber, Frank T1 - Resistance selection on antimicrobial surfaces N2 - Antimicrobial surfaces are widely used to reduce the number of bacteria residing in the indoor environment. In this talk, I discuss the risk how these surfaces can lead to the selection of antimicrobial resistant bacteria. T2 - Cost action workshop Amici - Antimicrobial Coatings Applied in Healthcare Settings – Efficacy Testing CY - BAM Unter den Eichen, Berlin, Germany DA - 07.06.2018 KW - Antimicrobial resistance KW - Antimicrobial surfaces KW - Cross-resistance PY - 2018 AN - OPUS4-46272 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Nordholt, Niclas A1 - Kanaris, Orestis A1 - Lewerenz, Dominique A1 - Gödt, Annett A1 - Schreiber, Frank T1 - Evolutionary implications of heterogeneous disinfectant tolerance N2 - Introduction: Effective disinfection is crucial to maintain hygiene and to prevent the spread of infections. Phenotypic heterogeneity in disinfection survival (i.e. tolerance) may result in failure of disinfection, which in turn may foster the evolution of resistance to both disinfectants and antibiotics. However, the consequences of phenotypic heterogeneity for disinfection outcome and resistance evolution are not well understood. Goal: This study investigates the impact of phenotypic heterogeneity on the survival and evolution of Escherichia coli during disinfection with six commonly used substances. Furthermore, the consequences of evolved disinfectant tolerance for antibiotic resistance evolution are studied. Materials & Methods: The extent of population heterogeneity during disinfection is derived by determining time-kill kinetics and analysis with mathematical modelling. The link between population heterogeneity and evolvability of disinfectant tolerance was assessed by laboratory evolution experiments under periodic disinfection. The ability of disinfectant tolerant strains to evolve antibiotic resistance is assessed by serial transfer experiments with increasing concentrations of different antibiotics and by whole genome sequencing. Results: Multi-modal time-kill kinetics in three of the six disinfectants suggest the presence of disinfectant-tolerant subpopulations (i.e. persister cells). Importantly, the ability and extent to evolve population-wide tolerance under periodic disinfection is related with the presence of persister cells and the level of phenotypic heterogeneity during disinfection. Interestingly, the probability of high-level resistance evolution to certain antibiotics is attenuated in disinfectant tolerant strains as compared to the sensitive ancestor. Whole-genome sequencing reveals epistatic interactions between disinfectant tolerance and antibiotic resistance mutations, preventing access to canonical evolutionary paths to resistance. Summary: Our findings suggest that phenotypic heterogeneity can facilitate disinfection survival and the evolution of population wide tolerance, which can impact future antibiotic resistance evolution. T2 - Vereinigung Allgemeiner und Angewandter Mikrobiobiologie Jahreskongress 2023 CY - Würzburg, Germany DA - 02.06.2024 KW - Biocide KW - Resistance KW - Persistence KW - Evolution KW - Herteogeneous phenotypes PY - 2024 AN - OPUS4-60244 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Schreiber, Frank T1 - Differential selection for survival and for growth in adaptive laboratory evolution experiments with benzalkonium chloride N2 - Biocides are used to control microorganisms across different applications, but emerging resistance may pose risks for those applications. Resistance to biocides has commonly been studied using adaptive laboratory evolution (ALE) experiments with growth at subinhibitory concentrations linked to serial subculturing. It has been shown recently that E. coli adapts to repeated lethal stress imposed by the biocide benzalkonium chloride (BAC) by increased survival (i.e. tolerance) and not by evolving the ability to grow at increased concentrations (i.e. resistance). Here, we investigate the contributions of evolution for tolerance as opposed to resistance for the outcome of ALE experiments with E. coli exposed to BAC. We find that BAC concentrations close to the half maximal effective concentration (EC50, 4.36 µg mL-1) show initial killing (~40%) before the population resumes growth. This indicates that cells face a two-fold selection pressure: for increased survival and for increased growth. To disentangle the effects of both selection pressures, we conducted two ALE experiments: (i) one with initial killing and continued stress close to the EC50 during growth and (ii) another with initial killing and no stress during growth. Phenotypic characterization of adapted populations showed that growth at higher BAC concentrations was only selected for when BAC was present during growth. Whole genome sequencing revealed distinct differences in mutated genes across treatments. Treatments selecting solely for survival led to mutations in genes for metabolic regulation (cyaA) and cellular structure (flagella fliJ), while treatments selecting for growth and survival led to mutations in genes related to stress response (hslO and tufA). Our results demonstrate that serial subculture ALE experiments with an antimicrobial at sub-inhibitory concentrations can select for increased growth and survival. This finding has implications for the design of ALE experiments to assess resistance risks of antimicrobials in different scenarios such as disinfection, preservation, and environmental pollution. KW - Antimicrobial resistance KW - Bacteria KW - Standardization KW - Biocides PY - 2024 UR - https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1074740 PB - National Library of Biotechnology Information CY - Bethesda AN - OPUS4-61559 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Schreiber, Frank A1 - Nordholt, Niclas T1 - Persistence against benzalkonium chloride promotes rapid evolution of tolerance under periodic disinfection N2 - Biocides used as disinfectants are important to prevent the transmission of pathogens, especially during the current antibiotic resistance crisis. This crisis is exacerbated by phenotypically tolerant persister subpopulations which can survive transient antibiotic treatment and facilitate resistance evolution. Despite the transient nature of disinfection, knowledge concerning persistence to disinfectants and its link to resistance evolution is currently lacking. Here, we show that E. coli displays persistence against a widely used disinfectant benzalkonium chloride (BAC). Periodic, persister-mediated failure of disinfection rapidly selects for BAC tolerance. BAC tolerance is associated with reduced cell surface charge and mutations in the novel tolerance locus lpxM. Moreover, the fitness cost incurred by BAC tolerance turned into a fitness benefit in the presence of antibiotics, suggesting a selective advantage of BAC-tolerant mutants in antibiotic environments. Our findings provide a mechanistic underpinning for the faithful application of disinfectants to prevent multi-drug-resistance evolution and to steward the efficacy of biocides and antibiotics. T2 - New Approaches and Concepts in Microbiology CY - Online meeting DA - 07.07.2021 KW - Persistence KW - Biocides KW - Evolution KW - Cross-resistance KW - Biocide tolerance PY - 2021 AN - OPUS4-53168 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Schreiber, Frank A1 - Kanaris, Orestis A1 - Nordholt, Niclas T1 - Consequences of benzalkonium chloride tolerance for selection dynamics and de novode novo resistance evolution driven by antibiotics N2 - Biocides are used in large amounts in industrial, medical, and domestic settings. Benzalkonium chloride (BAC) is a commonly used biocide, for which previous research revealed that Escherichia coli can rapidly adapt to tolerate BAC-disinfection, with consequences for antibiotic susceptibility. However, the consequences of BAC- tolerance for selection dynamics and resistance evolution to antibiotics remain unknown. Here, we investigated the effect of BAC -tolerance in E. coli on its response upon challenge with different antibiotics. Competition assays showed that subinhibitory concentrations of ciprofloxacin—but not ampicillin, colistin and gentamicin—select for the BAC-tolerant strain over the BAC-sensitive ancestor at a minimal selective concentration of 0.0013–0.0022 µg∙mL−1. In contrast, the BAC-sensitive ancestor was more likely to evolve resistance to ciprofloxacin, colistin and gentamicin than the BAC-tolerant strain when adapted to higher concentrations of antibiotics in a serial transfer laboratory evolution experiment. The observed difference in the evolvability of resistance to ciprofloxacin was partly explained by an epistatic interaction between the mutations conferring BAC -tolerance and a knockout mutation in ompF encoding for the outer membrane porin F. Taken together, these findings suggest that BAC -tolerance can be stabilized in environments containing low concentrations of ciprofloxacin, while it also constrains evolutionary pathways towards antibiotic resistance. KW - Antimicrobial surfaces KW - Biocides KW - Antimicrobial resistance KW - Antibiotics PY - 2025 UR - https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1282584 PB - National Library of Medicine CY - Bethesda AN - OPUS4-65221 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Schreiber, Frank A1 - Zimmermann, M. A1 - Escrig, S. A1 - Lavik, G. A1 - Kuypers, M.M.M. A1 - Meibom, A. A1 - Ackermann, M. T1 - Substrate and electron donor limitation induce phenotypic heterogeneity in different metabolic activities in a green sulphur bacterium N2 - Populations of genetically identical cells can display marked variation in phenotypic traits; such variation is termed phenotypic heterogeneity. Here, we investigate the effect of substrate and electron donor limitation on phenotypic heterogeneity in N2 and CO2 fixation in the green sulphur bacterium Chlorobium phaeobacteroides. We grew populations in chemostats and batch cultures and used stable isotope labelling combined with nanometer‐scale secondary ion mass spectrometry (NanoSIMS) to quantify phenotypic heterogeneity. Experiments in H2S (i.e. electron donor) limited chemostats show that varying levels of NH4+ limitation induce heterogeneity in N2 fixation. Comparison of phenotypic heterogeneity between chemostats and batch (unlimited for H2S) populations indicates that electron donor limitation drives heterogeneity in N2 and CO2 fixation. Our results demonstrate that phenotypic heterogeneity in a certain metabolic activity can be driven by different modes of limitation and that heterogeneity can emerge in different metabolic processes upon the same mode of limitation. In conclusion, our data suggest that limitation is a general driver of phenotypic heterogeneity in microbial populations. KW - NanoSIMS KW - Phenotypic heterogeneity PY - 2018 UR - https://onlinelibrary.wiley.com/doi/abs/10.1111/1758-2229.12616 DO - https://doi.org/10.1111/1758-2229.12616 SN - 1758-2229 VL - 10 IS - 2 SP - 179 EP - 183 PB - John Wiley & Sons Ltd AN - OPUS4-44596 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Schreiber, Frank T1 - Bakterielle Resistenzen und Toleranzen gegen Desinfektionsmittel und antimikrobielle Oberflächen N2 - Dieser Vortrag beschreibt die Entstehung von bakteriellen Resistenzen und Toleranzen gegen Desinfektionsmittel und antimikrobielle Oberflächen. T2 - Fachtagung für Krankenhaushygiene der Deutschen Gesellschaft für Krankenhaushygiene CY - Essen, Germany DA - 12.05.2023 KW - Antimikrobielle Resistenz KW - Antmikrobielle Oberflächen KW - Standardisierung KW - Biozide PY - 2023 AN - OPUS4-57860 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Schreiber, Frank T1 - Phenotypic diversity in microbial metabolism and antimicrobial resistance N2 - Most microorganisms live in environments where nutrients are limited and fluctuate over time. Cells respond to nutrient fluctuations by sensing and adapting their physiological state. Recent studies suggest phenotypic heterogeneity in isogenic populations as an alternative strategy in fluctuating environments, where a subpopulation of cells express a function that allows growth under conditions that might arise in the future. It is unknown how environmental factors such as nutrient limitation shape phenotypic heterogeneity in metabolism and whether this allows cells to respond to nutrient fluctuations. Here, we show that substrate limitation increases phenotypic heterogeneity in metabolism, and this heterogeneity allows cells to cope with substrate fluctuations. We subjected the N2-fixing bacterium Klebsiella oxytoca to different levels of substrate limitation and substrate shifts, and obtained time-resolved single-cell measurements of metabolic activities using nanometre-scale secondary ion mass spectrometry (NanoSIMS). We found that the level of NH4+ limitation shapes phenotypic heterogeneity in N2 fixation. In turn, the N2 fixation rate of single cells during NH4+ limitation correlates positively with their growth rate after a shift to NH4+ depletion, experimentally demonstrating the benefit of heterogeneity. The results indicate that phenotypic heterogeneity is a general solution to two important ecological challenges - nutrient limitation and fluctuations - that many microorganisms face. Currently, we use NanoSIMS to develop a new approach that defines functionally-relevant, phenotypic biodiversity in microbial systems. In the last part of my presentation, I will highlight why the concept of phenotypic diversity is relevant for the understanding of antimicrobial resistance. T2 - Berlin Seminar for Resistance Research at FU Berlin Veterinary Medicine CY - Berlin, Germany DA - 01.03.2018 KW - Antimicrobial Resistance KW - Metabolism KW - Phenotypic diversity PY - 2018 AN - OPUS4-44597 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Schreiber, Frank T1 - Biocides As Drivers For Antimicrobial Resistance Evolution In The Environment N2 - Antimicrobial resistance (AMR) is a global health problem with the environment being an important compartment for the evolution, selection and transmission of AMR. These processes are impacted by pollution with antibiotics. However, biocides used as disinfectants and material preservatives are major pollutants by far excceding the market for antibiotics in terms of mass. Our work shows that biocides have the potential to affect evolutionary processes towards AMR by increasing the rates of de-novo mutation and conjugation. These effects depend on the species and biocidal substance. Importantly, chlorhexidine and quaternary ammonium compounds (QACs) affect rates of mutation and conjugation at environmentally relevant concentrations in E. coli. Moreover, our results show a connection between the RpoS-mediated general stress and the RecA-linked SOS response with increased rates of mutation and conjugation, but not for all biocides. Furthermore, our work highlights the potential of biocides to contribute to selection and transmission of AMR. We show that the application of biocides, especially QAC disinfectants, leads to the rapid evolution of tolerance (i.e. increased survival) in adaptive laboratory evolution (ALE) experiments. The evolved tolerant strains have a selective advantage in the presence of environmentally-relevant concentrations of antibiotics, which could lead to the stabilization of biocide tolerance in environments where biocides and antibiotics co-occur (e.g. wastewater, animal stables). ALE experiments with biocide tolerant strains indicate a decreased evolvability of resistance to antibiotics. Taken together, our work shows the importance of assessing the contribution of biocides on evolution, selection and transmission of AMR in the environment. T2 - 6th Environmental Dimension of Antibiotic Resistance (EDAR6) CY - Gothenburg, Sweden DA - 22.09.2022 KW - Antimicrobial resistance KW - Antimicrobial coating KW - Biofilms KW - Biocides KW - Risk assessment PY - 2022 AN - OPUS4-56262 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Schmidt, Selina A1 - Rodríguez-Rojas, A. A1 - Rolff, J. A1 - Schreiber, Frank T1 - Biocides used as material preservatives modify rates of de novo mutation and horizontal gene transfer in bacteria N2 - Antimicrobial resistance (AMR) is a global health problem with the environment being an important compartment for the evolution and transmission of AMR. Previous studies showed that de-novo mutagenesis and horizontal gene transfer (HGT) by conjugation or transformation – important processes underlying resistance evolution and spread - are affected by antibiotics, metals and pesticides. However, natural microbial communities are also frequently exposed to biocides used as material preservatives, but it is unknown if these substances induce mutagenesis and HGT. Here, we show that active substances used in material preservatives can increase rates of mutation and conjugation in a species- and substance-dependent manner, while rates of transformation are not increased. The bisbiguanide chlorhexidine digluconate, the quaternary ammonium compound didecyldimethylammonium chloride, the metal copper, the pyrethroid-insecticide permethrin, and the azole-fungicide propiconazole increase mutation rates in Escherichia coli, whereas no increases were identified for Bacillus subtilis and Acinetobacter baylyi. Benzalkonium chloride, chlorhexidine and permethrin increased conjugation in E. coli. Moreover, our results show a connection between the RpoS-mediated general stress and the RecA-linked SOS response with increased rates of mutation and conjugation, but not for all biocides. Taken together, our data show the importance of assessing the contribution of material preservatives on AMR evolution and spread. KW - Mutation rate KW - Horizontal gene transfer KW - Biocides PY - 2022 DO - https://doi.org/10.1016/j.jhazmat.2022.129280 SN - 0304-3894 VL - 437 SP - 1 EP - 13 PB - Elsevier CY - Amsterdam AN - OPUS4-55261 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Schreiber, Frank T1 - Resistance evolution towards biocides and antimicrobial surfaces N2 - This talk discusses the work at BAM concerning Resistance evolution towards biocides and antimicrobial surfaces. It shows (i) that biocides affect rates of mutation and horizontal gene transfer, (ii) that biocides show heterogeneous killing facilitating tolerance evolution, and (iii) that biocides and antibiotics show strong combination effect on growth and selection. T2 - Exchange seminar with Nottingham Trent University CY - Berlin, Germany DA - 03.09.2024 KW - Antimicrobial resistance KW - Bacteria KW - Standardization KW - Biocides KW - Antimicrobial surfaces PY - 2024 AN - OPUS4-61548 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Schreiber, Frank T1 - Differential selection for survival and for growth in adaptive laboratory evolution experiments with benzalkonium chloride N2 - Biocides are used to control microorganisms across different applications, but emerging resistance may pose risks for those applications. Resistance to biocides has commonly been studied using adaptive laboratory evolution (ALE) experiments with growth at subinhibitory concentrations linked to serial subculturing. It has been shown recently that E. coli adapts to repeated lethal stress imposed by the biocide benzalkonium chloride (BAC) by increased survival (i.e. tolerance) and not by evolving the ability to grow at increased concentrations (i.e. resistance). Here, we investigate the contributions of evolution for tolerance as opposed to resistance for the outcome of ALE experiments with E. coli exposed to BAC. We find that BAC concentrations close to the half maximal effective concentration (EC50, 4.36 µg mL-1) show initial killing (~40%) before the population resumes growth. This indicates that cells face a two-fold selection pressure: for increased survival and for increased growth. To disentangle the effects of both selection pressures, we conducted two ALE experiments: (i) one with initial killing and continued stress close to the EC50 during growth and (ii) another with initial killing and no stress during growth. Phenotypic characterization of adapted populations showed that growth at higher BAC concentrations was only selected for when BAC was present during growth. Whole genome sequencing revealed distinct differences in mutated genes across treatments. Treatments selecting solely for survival led to mutations in genes for metabolic regulation (cyaA) and cellular structure (flagella fliJ), while treatments selecting for growth and survival led to mutations in genes related to stress response (hslO and tufA). Our results demonstrate that serial subculture ALE experiments with an antimicrobial at sub-inhibitory concentrations can select for increased growth and survival. This finding has implications for the design of ALE experiments to assess resistance risks of antimicrobials in different scenarios such as disinfection, preservation, and environmental pollution. KW - Antimicrobial resistance KW - Bacteria KW - Standardization KW - Biocides PY - 2024 DO - https://doi.org/10.5061/dryad.2jm63xszx PB - Dryad AN - OPUS4-61558 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Schreiber, Frank T1 - Selection of resistance by antimicrobials used in coatings N2 - Antimicrobial surfaces have broad use in multiple settings including touch surfaces in hospitals, implanted devices, or consumer products. Their aim is to support existing hygiene procedures, and to help combat the increasing threat of antimicrobial resistance. However, concerns have been raised over the potential selection pressure exerted by such surfaces, which might drive the evolution and spread of antimicrobial resistance. In my presentation, I will highlight the risks and knowledge gaps associated with resistance on antimicrobial surfaces by different processes including evolution by de novo mutations and horizontal gene transfer, and species sorting of inherently resistant bacteria dispersed onto antimicrobial surfaces. The latter process has the potential to select for antibiotic resistance via cross-resistance between traits that confer resistance to both the antimicrobial surface coating and antibiotics. Conditions in which antibiotics and antimicrobial coatings are present simultaneously (e.g. implants) will lead to more complex interactions that can either result in the selection for or against antibiotic resistance. We mapped these interactions between several antimicrobials and antibiotics on growth and selection of Pseudomonas aeruginosa. We find prevalent physiological (i.e. synergy and antagonism) and evolutionary (i.e. cross-resistance and collateral sensitivity) combination effects. Understanding these interactions opens the door to tailor therapeutic interventions to select against resistance. In additions, we need new methods and translational studies that investigate resistance development to antimicrobial surfaces under realistic conditions. Therefore, I will present recent developments in our lab on the development of such a method based on existing efficacy standards. T2 - 2021 Fall Meeting of the European Materials Research Society (E-MRS) CY - Online meeting DA - 20.09.2021 KW - Antimicrobial resistance KW - Antimicrobial coating KW - Biofilms KW - Biocides PY - 2021 AN - OPUS4-53645 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Schreiber, Frank T1 - Phenotypic diversity in microbial metabolism N2 - Most microorganisms live in environments where nutrients are limited and fluctuate over time. Cells respond to nutrient fluctuations by sensing and adapting their physiological state. Recent studies suggest phenotypic heterogeneity in isogenic populations as an alternative strategy in fluctuating environments, where a subpopulation of cells express a function that allows growth under conditions that might arise in the future. It is unknown how environmental factors such as nutrient limitation shape phenotypic heterogeneity in metabolism and whether this allows cells to respond to nutrient fluctuations. Here, we show that substrate limitation increases phenotypic heterogeneity in metabolism, and this heterogeneity allows cells to cope with substrate fluctuations. We subjected the N2-fixing bacterium Klebsiella oxytoca to different levels of substrate limitation and substrate shifts, and obtained time-resolved single-cell measurements of metabolic activities using nanometre-scale secondary ion mass spectrometry (NanoSIMS). We found that the level of NH4+ limitation shapes phenotypic heterogeneity in N2 fixation. In turn, the N2 fixation rate of single cells during NH4+ limitation correlates positively with their growth rate after a shift to NH4+ depletion, experimentally demonstrating the benefit of heterogeneity. The results indicate that phenotypic heterogeneity is a general solution to two important ecological challenges - nutrient limitation and fluctuations - that many microorganisms face. Currently, we use NanoSIMS to develop a new approach that defines functionally-relevant, phenotypic biodiversity in microbial systems. T2 - NanoSIMS user meeting CY - Utrecht, The Netherlands DA - 26.09.2016 KW - Stable isotopes KW - NanoSIMS KW - Metabolism PY - 2016 AN - OPUS4-37755 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Li, M. A1 - Schlaich, C. A1 - Zhang, J. A1 - Donskyi, Ievgen A1 - Schwibbert, Karin A1 - Schreiber, Frank A1 - Xia, Y. A1 - Radnik, Jörg A1 - Schwerdtle, T. A1 - Haag, R. T1 - Mussel-inspired multifunctional coating for bacterial infection prevention and osteogenic induction N2 - Bacterial infection and osteogenic integration are the two main problems that cause severe complications after surgeries. In this study, the antibacterial and osteogenic properties were simultaneously introduced in biomaterials, where copper nanoparticles (CuNPs) were generated by in situ reductions of Cu ions into a mussel-inspired hyperbranched polyglycerol (MI-hPG) coating via a simple dip-coating method. This hyperbranched polyglycerol with 10 % catechol groups’ modification presents excellent antifouling property, which could effectively reduce bacteria adhesion on the surface. In this work, polycaprolactone (PCL) electrospun fiber membrane was selected as the substrate, which is commonly used in biomedical implants in bone regeneration and cardiovascular stents because of its good biocompatibility and easy post-modification. The as-fabricated CuNPs-incorporated PCL membrane [PCL-(MI-hPG)-CuNPs] was confirmed with effective antibacterial performance via in vitro antibacterial tests against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and multi-resistant E. coli. In addition, the in vitro results demonstrated that osteogenic property of PCL-(MI-hPG)-CuNPs was realized by upregulating the osteoblast-related gene expressions and protein activity. This study shows that antibacterial and osteogenic properties can be balanced in a surface coating by introducing CuNPs. KW - Mussel-inspired coating KW - CuNPs KW - Multi-resistant bacteria KW - Antibacterial KW - Antifouling KW - Osteogenesis PY - 2021 DO - https://doi.org/10.1016/j.jmst.2020.08.011 SN - 1005-0302 VL - 68 SP - 160 EP - 171 PB - Elsevier Ltd. AN - OPUS4-51519 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -