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

Pathogenic bacteria are increasingly resistant to today’s antibiotics. Professor Gilles van Wezel seeks new forms of antibiotics in good bacteria that live in the soil.

Vancomycin is a last-resort antibiotic for the treatment of many Gram-positive bacterial infections, while remaining inactive against Gram-negative strains.

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…

How can efficient chemical synthesis and clinical microbiology be combined to identify new antibiotics against Clostridioides difficile infections?

With the rise of multi-drug resistant bacterial pathogens, the possibility of a post-antibiotic world is quickly becoming reality.

People who have taken antibiotics in the past three months pay more attention to negative facial expressions, according to research by postdoc Katerina Johnson and assistant professor Laura Steenbergen. This may explain how antibiotics increase the risk of developing depression.

Antibiotics are a class of medicine most people take for granted. But pathogenic bacteria are becoming more and more resistant to our antibiotics, and this poses a great challenge for future treatments. There is thus a great societal need to identify new molecules that can address new targets and be…

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…

Promotor: Prof.dr. G.P. van Wezel

Antimicrobial resistance is one of the biggest threats to human health worldwide in the coming decennia.

Antimicrobial resistance (AMR) is the phenomenon that pathogens become insensitive to the antibiotics that we use against them. A growing number of pathogens is becoming resistant, with methicillin-resistant S. aureus (MRSA) as the most famous example. But while the threat of AMR represents a slow-moving…

Bacteria are highly complex and diverse organisms that have adapted to survive in ecological niches ranging from the most extreme to the most heterogeneous environments.

Lecture

This thesis describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.

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.

PhD defence

The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.

Enzymes are innately sensitive to changes in the amino acid sequence, which largely constrains their evolutionary potential, i.e., evolvability. This evolutionary burden can be alleviated in the presence of stabilizing mutations, which increase the buffering capacity of enzymes to tolerate mutations…

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

This thesis tackles the urgent challenge of antimicrobial resistance (AMR) through the design of novel antibacterial agents.

Streptomyces are filamentous bacteria that produce more than two-thirds of known antibiotics.

Through his project we will unravel the global regulatory networks that control gene expression in Streptomyces bacteria and allow them to properly respond to major changes in the environment; we will then harness this knowledge to activate and identify novel antibiotics

Actinobacteria are Gram-positive bacteria that have a complex multicellular life cycle and are well known for their ability to produce a wide range of bioactive natural products (NPs).

PhD defence

Antibiotic-resistant bacteria pose a major health threat. Addressing this challenge requires among others the development of new antibacterial compounds. The research described in this thesis focuses on discovering novel antibiotics from soil bacteria, specifically Streptomyces and Paenibacillus.Despite…

Timely, adequate and optimal treatment of infectious diseases is essential for the survival of patients with bacterial infections (Surviving Sepsis campaign).

Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria.

Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle.

'What nature made isn’t necessarily an optimized medicine to use in the human body,’ says Professor of Biological Chemistry Nathaniel Martin. That’s why a group of Leiden researchers is making a chemistry-based improved version of the frequently used antibiotic vancomycin. They received an NWO NACTAR…

Streptomycetes are similar to moulds, but these bacteria live in the soil. They are very popular in biotechnology because they produce a great many antibiotics and enzymes. Gilles van Wezel will be using his Vici subsidy to study ways of increasing their production.

More and more people worldwide have infections caused by bacteria that are resistant to many types of antibiotic. Why is this and how big of a problem is it?

Increasing resistance and a lack of new antibiotics are a serious problem for public health. Against this background, Gilles van Wezel of the Institute of Biology Leiden is looking for new medicines. Together with former PhD student Changsheng Wu and colleagues he discovered the special antibiotic lugdunomycin,…

PhD student Doris van Bergeijk brought 40,000-year-old bacteria from mammoth poop back to life. She hopes to find new information that can help research at the Institute of Biology Leiden into antibiotics and antibiotics resistance. Read about it on European Antibiotic Awareness Day, 18 November.

Antibiotic resistance is a common problem among patients. The European Project TIPAT trains pharmacologists, microbiologists and immunologists of six universities in interdisciplinary thinking. The ultimate goal is to develop better treatment guidelines to combat resistance. Coen van Hasselt of the…

When a bacterium becomes more resistant to one antibiotic, it sometimes becomes more sensitive to another. To better understand this interaction, researchers from the Leiden Institute of Biology (IBL) and the Leiden Academic Center for Drug Research (LACDR) under supervision of Daniel Rozen and Coen…

Bacteria carry countless hidden treasures in their DNA: fragments that could hold the key to new medicines. But how do you pick out the most promising ones from millions of options? ‘Look at the switches that turn genes on and off,’ says molecular biologist Gilles van Wezel.

When you become very good at one thing, that sometimes comes at the expense of something else. Such trade-offs also apply to bacteria. When becoming more resistant to one antibiotic, bacteria can sometimes become more sensitive to another. Linda Aulin, PhD candidate in the pharmacology group of Coen…

Resistance to antibiotics is a major problem in health care. Thanks to a grant from the Elise Mathilde Fund and the LUF, pharmacologist dr. Coen van Hasselt can look for new dosing schedules to reduce the development of antibiotic resistance.

Current means of fighting bacteria are no longer as good as they used to be because of antibiotic resistance. These days, people are dying from bacterial infections that could have been cured fifty years ago.

No, this isn’t about a Star Wars Alliance that wants to suppress The Resistance. Rather, the EPIC Alliance brings together scientific experts from seven countries to address the growing threat of antibiotic resistance. Leiden professor Nathaniel Martin is part of the 11-member consortium.

Antibiotic resistance is an economic problem. Pharmaceutical companies cannot earn much from antibiotic research, so they do not invest in it. This makes it important that universities do so, says Ned Buijs.

When a bacterium becomes resistant to one antibiotic, it may sometimes become more sensitive to another. This biological side-effect offers an unexpected opportunity in the fight against antibiotic resistance.

Bacteriophages, viruses that infect bacteria, may be used as an alternative treatment option when antibiotics fail. Leiden researchers have studied the structure and function of a novel bacteriophage that could be used to treat one of the WHO bacterial strains of concern where new treatments are urgently…

Globally, the number of deaths from infections is on the rise as more bacteria become resistant to antibiotics. New classes are desperately needed. A promising resistance inhibitor is now being developed by the research group of Nathaniel Martin, Professor of Biological Chemistry. Inaugural speech on…

With the search for new antibiotics becoming increasingly urgent, artificial intelligence offers valuable help. Smart software developed by Leiden PhD candidate Alexander Kloosterman searched genomes of bacteria and found clusters of DNA that code for proteins that have an antibiotic effect. ‘This new…

Soil bacteria can produce a wealth of antibiotics that are new to us, claims Gilles van Wezel, Professor of Molecular Biotechnology at the Institute of Biology Leiden. His research group has developed a method that can rapidly identify and produce these unknown compounds.