TY - JOUR A1 - Trimpert, J. A1 - Groenke, N. A1 - Kunec, D. A1 - Eschke, K. A1 - He, Shulin A1 - McMahon, Dino Peter A1 - Osterrieder, N. T1 - A proofreading-impaired herpesvirus generates populations with quasispecies-like structure JF - Nature Microbiology N2 - RNA virus populations are composed of highly diverse individuals that form a cloud of related sequences commonly referred to as a ‘quasispecies’1–3. This diversity arises as a consequence of low-fidelity genome replication4,5. By contrast, DNA Virus populations contain more uniform individuals with similar fitness6. Genome diversity is often correlated with increased Fitness in RNA viruses, while DNA viruses are thought to require more faithful genome replication. During DNA replication, erroneously incorporated bases are removed by a 3′-5′ exonuclease, a highly conserved enzymatic function of replicative DNA but not RNA polymerases. This proofreading process enhances replication fidelity and ensures the genome integrity of DNA organisms, including large DNA viruses7. Here, we show that a herpesvirus can tolerate impaired exonucleolytic proofreading, resulting in DNA virus populations, which, as in RNA viruses8, are composed of highly diverse genotypes of variable individual fitness. This indicates that herpesvirus mutant diversity may compensate for individual Fitness loss. Notably, in vivo infection with diverse virus populations results in a marked increase in virulence compared to genetically homogenous parental virus. While we cannot exclude that the increase in virulence is caused by selection of and/or interactions between individual genotypes, our findings are consistent with quasispecies dynamics. Our results contrast with traditional views of DNA virus replication and evolution, and indicate that a substantial increase in population diversity can lead to higher virulence. KW - Marek's virus KW - Virulence KW - Quasispecies KW - Evolution PY - 2019 DO - https://doi.org/10.1038/s41564-019-0547-x SN - 2058-5276 N1 - Corrigendum: Nature Microbiology 4 (2019) 2025 VL - 4 SP - 2175 EP - 2183 PB - Nature Publishing Group CY - London AN - OPUS4-48896 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Sobisch, Lydia-Yasmin A1 - Schreiber, Frank T1 - Biocide resistance evolution of corrosion causing sulfate reducing bacteria N2 - SRB are environmentally and industrially important microorganisms. The disadvantage of their metabolic activity (e.g. sulfate reduction) results in the formation of toxic sulfide that leads to microbial influenced corrosion. SRB have been responsible for biocorrosion of ferrous metal. One of mitigation strategy is the use of biocides. However, it has been shown that various bacteria develop antimicrobial resistance due to excessive use of biocides. Thus, a deeper understanding of the evolution of biocide resistance of SRB is necessary. Three commonly used biocides, THPS, BAC, and GLUT were applied to investigate the susceptibility of Desulfovibrio alaskensis G20.The minimum inhibitory and bactericidal concentration and the killing kinetics of the three biocides was determined. These results will be used to conduct evolution experiments to determine the evolution of resistance towards biocides of SRBs. The outcome of this work can be helpful to improve the management of MIC treatments. T2 - Panel, Pitch & Popcorn by EUROMIC CY - Online meeting DA - 21.06.2021 KW - Biocide KW - Evolution KW - Mircobially influcenced corrosion KW - Sulfate reducing bacteria PY - 2021 AN - OPUS4-56940 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Schreiber, Frank A1 - Nordholt, Niclas A1 - Kanaris, Orestis A1 - Schmidt, Selina 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 - JOUR A1 - Plarre, Rüdiger T1 - Eine kleine kleine Natur- und Kulturgeschichte der Kleidermotte (Tineola bisselliella) JF - Sitzungsberichte der Gesellschaft Naturforschender Freunde zu Berlin N2 - A short natural and cultural history of the webbing clothes moth (Tineola bisselliella). It is generally accepted that the natural habitats of most pest insects can be found outside the synanthropic environment in layers of leaf litter, under bark, as well as in rodent or bird nests. Indeed, most of the common fabric pests have been reported as being facultative nidicolous. Therefore, infestation of commodities by pest insects out of these reservoirs is one possibility to be considered. However, the likelihood of a pest´s occurrence and survival outside of the synanthropic habitat largely depends on its ecological potential and competitiveness against other species of the same ecological guild. Some pest species are rarely found in wild habitats, especially in those regions where they are not native and where they have been introduced by man. The fabric pest Tineola bisselliella serves as a good example. Most likely originating from Central or Southern Africa, this insect was introduced into Europe probably not earlier than the late 18th century. Being more tolerant to dry environments than other fabric pests, its economical importance increased during the 20th century when the indoor climate changed because of central heating systems. Its occurrence in outdoor natural habitats must be regarded as accidental. Reported finds of webbing clothes moth larvae in bird nests e. g. have been largely overstated in the literature. Tineola bisselliella should be regarded as an invasive and eusynanthropic species in most parts of the world. KW - Textilschädling KW - Museumsschädling KW - Anpassung KW - Evolution PY - 2018 SN - 0037-5942 VL - Neue Folge 53 SP - 43 EP - 57 PB - Gesellschaft Naturforschender Freunde zu Berlin CY - Berlin AN - OPUS4-44048 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Nordholt, Niclas A1 - Schreiber, Frank A1 - Kanaris, Orestis A1 - Schmidt, Selina 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 - World Microbe Forum (ASM, FEMS) CY - Online meeting DA - 20.06.2021 KW - Persistence KW - Biocides KW - Evolution KW - Cross-resistance KW - Biocide tolerance PY - 2021 AN - OPUS4-53167 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Nordholt, Niclas A1 - Kanaris, Orestis A1 - Schmidt, Selina A1 - Schreiber, Frank T1 - Persistence against benzalkonium chloride promotes rapid evolution of tolerance during periodic disinfection JF - Nature Communications 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 that can survive transient antibiotic Treatment and facilitate resistance evolution. 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, which is associated with reduced cell Surface charge and mutations in the lpxM locus, encoding an enzyme for lipid A biosynthesis. Moreover, the fitness cost incurred by BAC tolerance turns into a fitness benefit in the presence of antibiotics, suggesting a selective advantage of BAC-tolerant mutants in antibiotic environments. Our findings highlight the links between persistence to disinfectants and resistance evolution to antimicrobials. KW - Persistence KW - Biocides KW - Evolution KW - Cross-resistance KW - Biocide tolerance KW - Disinfection PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-538532 DO - https://doi.org/10.1038/s41467-021-27019-8 SN - 2041-1723 VL - 12 IS - 1 SP - 6792 PB - Springer AN - OPUS4-53853 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 - CONF A1 - Nordholt, Niclas T1 - EVOCIDE: Preserving disinfectant efficacy by predicting evolution: exposing the principles of disinfectant survival and adaptation in bacteria N2 - Presentation of the EVOCIDE research proposal work programme.EVOCIDE seeks to gain a systems level understanding of disinfectant survival and evolution in bacteria. T2 - Joint Group Seminar Rolff-McMahon-Armitage-Steiner CY - Berlin, Germany DA - 20.12.2023 KW - Disinfectants KW - Evolution KW - Microbiology KW - Bacteria KW - Biocides PY - 2023 AN - OPUS4-59224 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Nordholt, Niclas A1 - Schreiber, Frank T1 - Heterogeneous tolerance to biocides and its consequences for the evolution of antimicrobial resistance N2 - The exposure to antimicrobial substances drives the evolution of antimicrobial resistance (AMR). Biocides are antimicrobials used as disinfectants, antiseptics and preservatives. They find application on a large scale in the industrial and medical sector, but also in private households. In terms of mass, the worldwide use of biocides exceeds that of antibiotics. Thus, despite their important role in preventing the spread of pathogens, due to their ubiquity, biocides are suspected to be drivers of the antimicrobial resistance crisis. In our work we try to understand how biocides contribute to the emergence of AMR, what the underlying adaptation principles and mechanisms are and how they compare to those found for antibiotics. Here, I present results which demonstrate that phenotypic heterogeneity in E. coli, namely the formation of tolerant persister cells, can enable the survival of disinfection and consequentially facilitate the evolution of AMR. Using experimental evolution that selects for tolerance, we find that mutations in lipid A biosynthesis arise following periodic treatment with benzalkonium chloride (BAC), a widely used disinfectant. BAC tolerance is associated with additional, diverse mutations as well as changes in the susceptibility to antibiotics from different classes and changes in motility and biofilm formation, suggesting extensive regulatory re-wiring in the evolved clones. Remarkably, we find that fitness costs (growth rate reduction) incurred by BAC tolerance are alleviated in the presence of antibiotics. These findings demonstrate the complexity underlying the adaptation to antimicrobials and highlight the links between persistence to disinfectants and resistance evolution to antimicrobials. T2 - 4th VAAM discussion meeting 'Microbial Cell Biology' CY - Berlin, Germany DA - 09.10.2022 KW - Persistence KW - Biocides KW - Evolution KW - Disinfection KW - Biocide tolerance KW - Heterogeneity PY - 2022 AN - OPUS4-55958 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Nordholt, Niclas A1 - Kanaris, Orestis A1 - Schmidt, Selina A1 - Schreiber, Frank T1 - Persistence against benzalkonium chloride promotes rapid evolution of tolerance under periodic disinfection N2 - A presentation given at the VAAM conference 2022, summarizing our findings published in the research paper "Persistence against benzalkonium chloride promotes rapid evolution of tolerance under periodic disinfection" T2 - Annual conference of the association for general and applied microbiology (VAAM) 2022 CY - Düsseldorf, Germany DA - 21.02.2022 KW - Persistence KW - Biocides KW - Evolution KW - Cross-resistance KW - Biocide tolerance KW - Disinfection PY - 2022 AN - OPUS4-54437 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -