This thesis describes the evaluation of novel natural products with antibacterial activity enabled by total chemical synthesis.

Given the accelerating appearance of antimicrobial resistance, there is an urgent need for more fundamental research into novel antibiotic strategies. The work in this thesis helps to address this global problem by developing new antibiotic compounds, inspired by the antibacterial mechanisms of the…

The investigations described in this thesis lay out strategies aimed at advancing antibiotic research and development. The examples presented revolve around two main approaches: understanding drug-target interactions and target identification.

The impact of the phenotypic plasticity of P. aeruginosa and the distinct CF lung microenvironments on antibiotic drug effects and resistance remains poorly understood.

Polymyxins are clinically used antibiotics, discovered in mid-20th century. Once abandoned due to excessive nephrotoxicity, they are now used increasingly to address infections caused by multi-drug resistant Gram-negative bacteria.In this thesis, we describe the development and synthesis of analogues…

Antibioticaresistentie is een van de grootste bedreigingen wereldwijd voor de volksgezondheid in de komende decennia.

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

Promotor: G.P. van Wezel, Co-promotor: Y.H. Choi

The soil-dwelling, filamentous bacteria of the genus Streptomyces are renowned for their production of useful secondary metabolites including antibiotics. The work described in this thesis provides new insights on the role and regulation of antibiotic production and resistance in these bacteria.

This thesis examines strategies to address the global threat of antimicrobial resistance (AMR). Antimicrobial resistance poses an increasing global health risk, highlighting the need for new treatments against Gram-negative pathogens.

The ongoing increase in antimicrobial resistance combined with the low discovery of novel antibiotics is a serious threat to our health care.

Obesity may alter how a person absorbs, distributes, metabolizes or excretes medication. This thesis describes how obesity affects drug levels in the blood for antimicrobial agents, such as ciprofloxacin and fluconazole.

Promotor: G.P. van Wezel

Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)

Hoe kunnen we efficiënte chemische synthese en klinische microbiologie combineren om nieuwe antibiotica tegen Clostridioides difficile-infecties te ontwikkelen?

β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination…

Wanneer een bacterie resistenter wordt voor het ene antibioticum, wordt het soms gevoeliger voor een ander. Om deze wisselwerking beter te begrijpen, brachten onderzoekers van het Instituut Biologie Leiden (IBL) en het Leiden Academic Centre for Drug Research (LACDR) onder leiding van Daniel Rozen en…