GUPEA

Gothenburg University Publications Electronic Archive

GUPEA is a platform for e-publishing of theses, student essays and other research publications.

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  • Studentertoget til Kristiania i 1869 /
    (1869) Borchsenius, Otto,
  • From Marine Actinobacteria to Synthetic Analogues: Exploring Natural and Engineered Peptides and Peptidomimetics for their Antimicrobial Potential
    (2026-01-14) Beyer, Luisa
    Marine microorganisms constitute a largely untapped reservoir of structurally diverse and biologically active secondary metabolites, including antimicrobial peptides. These are promising alternatives to conventional antibiotics in the context of increasing antimicrobial resistance. This PhD thesis combines genome mining, chemical synthesis, metabolomics, and mechanistic investigations to explore the biosynthetic potential of marine-derived actinomycetes. Special emphasis is put on elucidating the structure-activity relationships and modes of action of novel antimicrobial peptides. Genome mining of Streptomyces sp. H-KF8, an Actinomycetota isolated from a remote Patagonian fjord in northern Chile, revealed multiple biosynthetic gene clusters predicted to encode nonribosomal peptides with antimicrobial activity. Guided by these predictions, several peptides, including cyclic variants, were rationally designed, chemically synthesized, and evaluated for antimicrobial activity. Two non-cytotoxic, non-lytic, and serum-stable peptides interacted with the bacterial cell membrane, allowing ion passage and dissipating the membrane potential. Despite close structural similarity determined by NMR spectroscopy, minor sequence modifications resulted in pronounced differences in antimicrobial activity and mechanism of action. Mechanistic analyses in Escherichia coli, including quantitative proteomics, in vitro transcription-translation assays, and DNA binding, indicate that antimicrobial activity primarily results from interference with central information-processing pathways. Further structural changes produced a focused library of peptide variants, several of which showed substantially improved activity against clinically relevant pathogens. Single amino acid substitutions markedly influenced antimicrobial potency and mechanism of action. In addition, actinomycetes isolated from a marine sponge included a putative novel Salinispora species. Metabolomic and genomic analyses of strain CH2A1_6 revealed antimicrobial activity and rare NRPS biosynthetic gene clusters, highlighting the potential of marine actinomycetes as a source of novel antimicrobial scaffolds.
  • Nicotine-induced neuroplasticity in amygdalo-striatal circuits
    (2026-01-14) Erika Lucente
    Nicotine addiction emerges from widespread neurobiological adaptations across reward-, habit-, and emotion-related circuits, yet the mechanisms driving these changes, especially sex-dependent ones, remain insufficiently understood. This thesis investigates acute and chronic nicotine-induced neuroplasticity in subregions of the striatum and amygdala, with emphasis on astrocytic involvement and sex-specific adaptations. Studies involved a battery of techniques including ex vivo electrophysiology, in vivo microdialysis, slice cyclic voltammetry, slice photometry, proteomics, immunohistochemistry and behavioral assays. Overall, this thesis demonstrates that nicotine elicits a sex-independent and α4β2-dependent long-term depression (nic-LTD) at excitatory synapses in the dorsolateral striatum (DLS), an effect associated with impaired astrocyte function. Nicotine further facilitates LTD elicited by high frequency stimulation (HFS-LTD) in the DLS of female rats, which might promote the establishment of a nicotine taking habit. Following repeated exposure, however, a tolerance to nicotine develops and the influence of dopamine over LTD induction is transformed. During the abstinence phase, excitatory neurotransmission remains depressed, and the effect by 5-HT on neurotransmission is altered in a differential manner in distinct striatal subregions, putatively influencing emotional processing. A hypoglutamatergic state is further observed selectively in the female basolateral amygdala. This neuroplasticity may further contribute to negative effect during nicotine abstinence and reduce the chances of nicotine cessation. Thus, nicotine produces selective neuroplasticity, and the female brain appears to be especially vulnerable. Sex-specific strategies for reducing nicotine dependence may thus be warranted.