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…

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

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…

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

'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.

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.

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.

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.

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.

Biological chemist Nathaniel Martin is going to test an alternative antibiotic that can combat common resistant bacteria such as MRSA. For this purpose, he will receive 350,000 euros from the NWO's NACTAR programme. ‘We want to know how safe and effective our antibiotic is in a realistic situation.’

An international consortium of research groups is aiming to develop novel antibiotics against the tuberculosis bacteria and two other deadly bacteria. The European Union has awarded a total of 18 million euros to the RespiriTB and RespiriNTM projects. Researchers from the Leiden University Medical Centre…

Prof. Gilles van Wezel and Prof. Mike Richardson of the Institute of Biology Leiden received €1.4 million to find new antibiotics.

Optimised antibiotic combinations can combat bacteria more effectively while also slowing the development of resistance. Scientists from five European countries are joining forces to identify such combinations and provide tools for others to do the same. The project is led by Professor Coen van Hasselt…

Collaborating and learning from other fields – that is what bioinformatician Hannah Augustijn enjoys most about doing research. During her PhD at Leiden University, she developed new ways to search within bacteria for the antibiotics of the future.

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.

We aim to engineer streptomycetes to fully exploit their potential for natural product productions, by a rational design and evolution approach.

Leiden researcher Anne-Grete Märtson brought together a large number of studies to better understand antibiotic dosing in patients with obesity. The publication in a renowned medical journal has already garnered much positive reactions, Märtson says. ‘It’s high time researchers started sharing more…

The antibiotic EVG7, developed in Leiden, has proven capable of fighting the dangerous gut bacterium C. difficile with only a minimal dose. What’s more, the bacterium is far less likely to return, a major issue with existing antibiotics. The research was published in Nature Communications.

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.

There are millions of gene clusters that encode the biosynthesis of bioactive natural products, with the vast majority yet unknown. How can we prioritize them to discover new chemical space for antibiotics? For this we will set up a pipeline based on federated learning (AI), synthetic biology and bioactivity…

This multidisciplinary project aims to deliver new antibiotics to target the WHO priority pathogen Klebsiella pneumoniae, one of the most dangerous pathogens in the clinic today.

Researchers in Leiden have, for the first time, observed how a specialised enzyme helps bacteria stay alinve when oxygen levels are low, and how that process can be blocked. The discovery opens up new possibilities for targeted antibiotics.

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.

Professor Biological chemistry Nathaniel Martin from the Institute of Biology Leiden is interviewed by the Netherlands Innovation Network on innovative scientific approaches. He talks about his work on designing new antibiotics and developing new molecules to make resistant bacteria susceptible again…

German scientists and NASA have developed a bacteria-killing coating for space toilets. With this coating they hope to protect astronauts in space stations from pathogens. Professor of Biological chemistry Nathaniel Martin sheds light on the discovery: 'You don't expect nasty bacteria up there, but…

Promotor: G.P. van Wezel

The death of his grandfather in 1988 motivates Changsheng Wu to become a scientist. In 2016, he is awarded the C.J. Kok Jury Award for his thesis on novel antibiotics. Two years later, he will become a Professor at Shangdong University, at the age of 30 years.

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

Leiden Biology student Lukas Kiefer has won the Unilever Research Prize 2018 for his research into efficient production of a new antibiotic. Kiefer: ‘I want to make biological medicines available to people in need.'

The adventure of iGEM Leiden has come to an end. The result: prizes for Best Therapeutic Project and Best Model, a gold medal, a successful crowdfunding campaign and of course their open-source research findings, which are available for the scientific community.

Cryogenic memories, antibiotic treatment for urinary tract infections and recycling plastic sustainably. These are the subjects of the three NWO-XS grants awarded to Leiden Science researchers.

Daniel Rozen (45), at the IBL since September 2012, uses bacteria in laboratory tests on experimental evolution to study the ecology and genetics of adaptation. His research has applied importance, as it reveals how bacteria may be induced to produce new antibiotics. Last January, Rozen received the…

Two consortia led by Leiden researchers have been awarded over one million euros by the Dutch Research Council and the Ministry of Health, Welfare and Sport to find solutions to antimicrobial resistance.