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

Gubbens

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.

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…

Can the pink-pigmented microbe Methylobacterium extorquens be genetically engineered to convert the sustainable raw material methanol into antibiotics?

Utilization of plant-originated products as new antibiotics

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.

How can cell wall engineering approaches be used to improve streptomycetes for industry to make new antibiotics?

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…

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.

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.’

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

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…

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…

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

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.

Can animal venoms yield novel antimicrobial peptides?

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

Biosynthetic gene clusters (BGCs) for natural products are widespread in microbial genomes, and they are rapidly exchanged. This research assesses the factors that control the spread of BGCs and resistance genes in nature. This includes risk assessment for the spread of engineered DNA in nature.

Is it possible to synthesize industrially relevant compounds in a sustainable manner through the use of light-capturing cyanobacteria?

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…

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…

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.

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.'

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…

From a new generation of antibiotics and more-effective vaccines to a map of dark matter and new light on Hindu traditions. Four researchers from Leiden University have received a prestigious €2.5m ERC Advanced Grant to develop their research.

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…

Fighting against cancer, antibiotic resistance and disposable plastics: Ahmed Ali, Fredj Ben Bdira, and Valerio Barbarossa receive a LUF grant for their innovative and socially relevant research. These grants for academic talent are often an important step towards grants by NWO and other grant insti…

Thread-like bacteria make cells that no longer have a cell wall under the influence of osmotic stress. A remarkable discovery, since the cell wall serves as a protection barrier for bacteria. It could also help to explain how pathogenic bacteria can hide in our body from our immune system. A team of…