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Unravelling novel modes of antimicrobial action
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The work presented in this thesis aimed at unravelling novel modes of
antimicrobial action through: i) the study of Staphylococcus aureus defences
against nitric oxide, an antimicrobial weapon of the innate immune system, namely
by performing the biochemical characterisation of S. aureus NO-detoxifying
flavohaemoglobin and analysing the conditions under which the enzyme is
operative; ii) the identification of the mechanisms beyond the antibacterial activity
of azole antibiotics towards S. aureus that were shown to include the increase of
endogenous reactive oxygen species triggered by the binding of imidazoles to
flavohaemoglobin; and iii) the discovery of a novel type of bactericides, the carbon
monoxide-releasing molecules, and identification of its potential cellular targets via
analysis of the transcriptional response of Escherichia coli to CORM-2, a carbon
monoxide-releasing molecule known to mimic the physiological function of carbon
monoxide.(...)
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Dissertation presented to obtain the Ph.D. degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa
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Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa