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

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.

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,…

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.

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.

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.

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.

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

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.'

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…

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…

After four years of hard work, the time has finally come: your thesis is finished. But who of your family and friends will ever read it? Biologist Lizah van der Aart decided to make a magazine for layman. 'It was precisely the explanation of the difficult, fundamental parts that gave me good tools for…

We investigate bacteria and fungi to understand their malicious or beneficial impact on food crops and their pathogenic or antibiotic role in human health.

Though tuberculosis can be cured today, new resistant strains of the bacteria are becoming a growing problem in the medical world. Biologist Annemarie Meijer and her colleagues are studying resistance to this disease. Their research is already yielding several interesting clues that could help the development…

On 1 August, Lars Jeuken started work as Professor of Biophysical Chemistry at the Leiden Institute of Chemistry (LIC). His research is at the intersection of biology and chemistry, but also involves physics and nanotechnology. Jeuken: ‘By linking nanoparticles to proteins and bacteria, we want to convert…