Treatment options for infections caused by antimicrobial-resistant bacteria are rendered ineffective, and drug alternatives are needed - either from new chemical classes or drugs with new modes of action. Historically, natural products have been important contributors to drug discovery. The search for new antimicrobials from marine fungi led to the discovery of the dimeric naphthopyrone lulworthinone produced by an obligate marine fungus in the family Lulworthiaceae (Jenssen et al. ,2021). The observed potent antibacterial activity against Gram positive bacteria, including several clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, promoted this follow-up mode of action investigation. Lulworthinone treatment induced an upregulation of genes responding to cell envelope stress in Bacillus subtilis. Further in vitro assays, focusing on membrane integrity and membrane potential, indicated that the compound is active on the bacterial membrane without destroying it. This was supported by NMR experiments using artificial lipid bilayers. Fluorescence microscopy revealed that lulworthinone affects cell morphology and interferes with the localization of the cell division protein FtsZ which might lead to impaired cell division. Surface plasmon resonance spectrometry and dynamic light scattering assays showed that this activity is linked with the compound's ability to form colloidal aggregates. Antibacterial agents targeting the bacterial membrane are of special interest since resistance development against such compounds seems harder to achieve and sustain.

This dataset is consists of six zip files containing the results from in vivo assays focused on biosensors, membrane integrity, membrane potential, Time-kill curves; pharmacodynamic modelling and microscopy pictures.

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