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Title [sv]
Utveckling av Virulensblockerande Antibiotika
Title [en]
Development of Drugs to Block Bacterial Virulence Factors
Abstract [en]
Bacterial pathogens resistant to antibiotics are a major public health problem. Therefore alternatives to antibiotics are urgently needed. To address this, we perform fundamental and applied research on the molecular mechanisms that govern bacterial virulence. Our aim is to develop novel, small-molecule therapies to combat bacterial infections by targeting key virulence factors. Our work focuses on the intracellular Listeria monocytogenes (L.m.)—a major foodborne human pathogen. We perform structure-function studies of PrfA, the master regulator of virulence gene expression that is central for converting L.m. from a soil-growing to a human pathogenic bacteria. We have identified lead compounds that inhibit PrfA and attenuate L.m. virulence. We aim to develop these lead compounds into drug candidates with optimized target engagement and improved pharmacokinetic properties. During the infection process, PrfA is tightly regulated by a number of environmental cues, e.g. peptides, oxidative stress, and temperature. We will explore how these cues regulate PrfA at the molecular level to gain a complete understanding of PrfA allosteric activity and expression, and exploit this knowledge to guide our drug design. Furthermore, many other pathogens contain PrfA-like transcriptional activators. The fundamental principles that emerge from understanding L.m. PrfA could therefore be applicable to them as well.
Principal InvestigatorSauer-Eriksson, Elisabeth
Coordinating organisation
Umeå University
Funder
Period
2020-01-01 － 2023-12-31
National Category
Structural BiologyBiochemistry and Molecular Biology
Identifiers
DiVA, id: project:2137Project, id: 2019-03771_VR

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Structural BiologyBiochemistry and Molecular Biology

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