Potentiation of Gram-positive specific antibiotics against Gram-negative bacteria through outer membrane disruption

Wesseling, C.M.J. (2022)

Doctoral Thesis

Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria. Classes of antibiotics otherwise limited to the treatment of Gram-positive pathogens may be potentiated against Gram-negative bacteria by disruption of their outer membrane. The work described in this thesis focuses on the development of novel synergists designed to selectively disrupt the outer membrane and in doing potentiate the activity of antibiotics that are otherwise inactive against Gram-negative bacteria.

• Biological Chemistry
• Synergy
• Outer membrane disruption
• Gram-negative bacteria
• Structure–activity relationship studies
• Bis-amidines
• Checkerboard assays
• Fractional inhibitory concentration index (FICI)

• All authors: Wesseling, C.M.J.
• Supervisor: Martin, N.I.; Rooijakkers, S.H.M.
• Committee: Wezel, G.P. van; Claessen, D.; Kasteren, S.I. van; Sorge, N.M. van; Kuipers, O.P.
• Qualification: Doctor (dr.)
• Awarding Institution: Institute of Biology Leiden (IBL), Faculty of Science, Leiden University
• Date: 2022-07-05
• ISBN (print): 9789464217704