It has become increasingly clear that low levels of antibiotics present in many environments can select for resistant bacteria, yet the evolutionary pathways for resistance development during exposure to low amounts of antibiotics remain poorly defined. 9, no 1, article id 1599 Article in journal (Refereed) Published Abstract , B41, Husargatan 3, Uppsala, 13:00 (English)

Microbiology Evolutionary Biology Identifiers URN: urn:nbn:se:uu:diva-355532 ISBN: 978-9-0 (print) OAI: oai::uu-355532 DiVA, id: diva2:1229526 Public defence 59 Seriesĭigital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 1477 Keywords Īntibiotic resistance evolution, Escherichia coli, Salmonella, porins, fitness, epistasis, strain-specificity, sub-MIC, de novo gene evolution National Category Place, publisher, year, edition, pagesUppsala: Acta Universitatis Upsaliensis, 2018. Understanding these factors in detail will enable us to better predict and prevent the emergence of antibiotic resistance development, through improvements in surveillance, treatment regimens and drug development. The studies presented in this thesis provide insights into the mechanistic basis of resistance evolution, including the mutational spectrum causing antibiotic resistance, compensatory pathways for growth-restoration and the influence of epistatic interactions on the phenotypic expression of resistance mutations. This demonstrates that new genes can arise from pools of non-coding sequences and that this process is relatively common. Finally, we show that aminoglycoside resistance genes can be selected de novo from the expression of completely randomized nucleotide sequences. Despite these low concentrations and weak selective pressure, strains of Salmonella Typhimurium evolved high-level resistance, which followed completely different mutational pathways compared to high-level selection. In contrast, strong epistatic interactions were observed in mutants evolved at sub-lethal concentrations of streptomycin. However, outliers from this trend exemplify the limitations of solely relying on laboratory strains for the characterization of antibiotic resistance mechanisms. Furthermore, we demonstrate that the phenotypic effects of antibiotic resistance mutations are largely predictable, both in combination with each other as well as in different bacterial strains.

Using porin-deficient mutants of Escherichia coli, we show that upregulation of alternative porins provides compensatory mechanisms that can ameliorate the fitness costs associated with resistance. Here, we investigate the factors that govern how antibiotic resistance mechanisms affect bacterial fitness and the overall level of resistance. For this, we need to acquire a deeper understanding of the mechanisms underlying the evolution of antibiotic resistance. Thus, we need to find ways to reduce the rate of antibiotic resistance development. The development of new antibiotics is slow and cannot counterbalance the dissemination of resistant bacteria. The continuing emergence and spread of antibiotic resistant bacteria are a threat to various applications in modern medicine and impose a strong economic burden on health systems. My philosophy is to give back to my communities - drop me a line for details on a fundraiser campaign?ĭrop us a note to share how you use them to receive a 15% discount coupon on a future order.2018 (English) Doctoral thesis, comprehensive summary (Other academic) Abstract I wish you all the best and don’t forget to toss them in your dishwasher or washer (with jeans or non-delicate items).

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