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Mode of action of antimicrobial lipopeptides produced by Bacillus subtilis
Pinkas, Dominik ; Seydlová, Gabriela (advisor) ; Žíla, Vojtěch (referee)
Increasing bacterial resistance to classical antibiotics and emergence of multi-resistant strains impose a constant threat. Antimicrobial compounds of bacterial origin are an important source of new antibacterial therapeutic agents needed to answer this issue. Three families of lipopeptides produced by Bacillus subtilis - surfactins, fengycins and iturins represent an interesting class of such compounds. They exert a wide range of biological activities and possess a good potential for modifications and improvement of their structure and function. Lipopeptides produced by B. subtilis are surface active compounds capable of reducing surface/interface tension. The variety of their biological activities stems from their ability to insert into lipid membranes leading to disruption and permeabilization of the membrane. Specific mode of action differs between the three families but the common feature is that it is concentration dependent. First, lipopeptides induce ion leakage, pore formation and then the increasing concentration eventually causes complete solubilisation of the membrane in a detergent-like manner. In addition, surfactin can inhibit some enzymes by chelating divalent cations required for their activity. These properties make the B. subtilis lipopeptides promising compounds for commercial applications.
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Genomic preferences in integration and expression of retroviruses and retrovirus-derived vectors
Miklík, Dalibor ; Hejnar, Jiří (advisor) ; Žíla, Vojtěch (referee)
Integration and provirus establishment are the key steps of retroviral life cycle. Genome-wide studies show that the integration is not a random process and that groups of related retroviruses display distinguishable patterns of integration preferences. The most rated genomic features forming the integration preferences of retroviruses are transcription units, transcription start sites and CpG islands. Whereas extending knowledge of genome structure, new, mainly epigenetic marks, which have a relationship to retroviral preferences are being defined. The integration into a specific genome region has a straight influence on the provirus expression and therefore on the production of virus progeny. While integration into some regions results in provirus silencing which is managed and maintained by variety of factors, some other genomic regions are vice-versa capable of stable provirus expression maintenance. These findings have implications for construction of safe and efficient retroviral vectors as well as for use of modified retroviruses as markers for an epigenetic and expression profile determination of genome regions.
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