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Matthias Willmann wants to get the big picture – tracking down infectious agents

While fighting and curing bacterial infections in sick patients is one part of the picture, epidemiological investigation of the spread of pathogens is another. Dr. Matthias Willmann also assesses the impact of these factors on the healthcare system as a whole and draws conclusions that might boost early detection of pathogens and prevention of infections.

Prof. Dr. Matthias Willmann has been junior professor in Tübingen since early 2016 and investigates nosocomial bacterial infections, i.e. infections that are acquired in hospital. © private

“Curiosity is a powerful driver of learning as Prof. Dr. Matthias Willmann’s career clearly illustrates. During his medical studies at the University of Göttingen, Willmann travelled the world and gained research experience in exotic places, including the All India Institute of Medical Sciences, New Delhi, India, and the Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania, where he obtained insights into tropical medicine and a broad range of pathogens. After returning home, Willmann decided to turn his hand to science with a doctorate at the Max Planck Institute for Biophysical Chemistry in Göttingen. His doctoral thesis was on the intracellular transport of SNARE proteins (SNARE = soluble N-ethylmaleimide-sensitive-factor attachment receptor), which are involved in the vesicle-associated release of neurotransmitters in nerve cells.

In 2009, with a doctoral degree under his belt, Willmann turned to medicine once again, applying for a position as assistant doctor in the Department of Infectious Diseases at the Comprehensive Infectious Diseases Centre at the University of Ulm in Baden-Württemberg where he worked mainly on tropical medicine. “When I was doing my doctorate at the Max Planck Institute, I had the opportunity to experience what working at a lab bench and doing experiments was like. As a matter of fact, I have always been interested in scientific laboratory work, but never wanted to lose sight of the patient. I always dreamt of combining patient contact with practical lab work.”

Willmann had already studied the mechanisms pathogens use to spread in the population and was seeking ways to fight epidemics and prevent the epidemic spread of infections. However, he was after an even broader picture than usual. “I was intrigued by the idea of studying the potential effects tropical diseases might have on the healthcare system and the economy as a whole. How they might slow down a country's development, for example,” said Willmann. In 2010, to quench his thirst for scientifically sound knowledge and to further develop his expertise, Willmann decided to continue his career in London. He obtained an MSc in tropical medicine and international health at the London School of Hygiene and Tropical Medicine and a diploma degree in tropical medicine and hygiene at the Royal College of Physicians. “The master’s programme consisted mainly of epidemiological training related to international health, where, amongst other things, I learned about the tools needed for designing clinical trials. The diploma degree course focused specifically on clinical issues such as the diagnosis of tropical diseases. The two courses were very compact, which is why I was able to do both at the same time,” said Willmann.

The most important reason for Willmann’s success: a broad knowledge base

Pseudomonas aeruginosa bacteria are cultivated on blood agar plates. The genetic analysis of different isolates enables conclusions to be drawn on how the bacteria spread in hospitals, for example. © Willmann, Tübingen University Hospital

Since 2011, Willmann has headed up the Clinical Microbiology and Epidemiology of Infectious Diseases research group at the Institute of Medical Microbiology and Hygiene at Tübingen University Hospital. Here, Willmann is able to utilise his broad range of knowledge on different levels. His team is specifically focused on the genomics of infections acquired in healthcare institutions using state-of-the-art methods like next-generation sequencing (NGS), which in recent years has become a highly effective and indispensable tool for investigating the spread of infections. Willmann explains the benefits of NGS: “Bacteria have short generation times and accumulate many DNA errors as they spread. We sequence and compare the genome of bacteria from different patient isolates. This allows us to deduce likely transmission paths. If the bacteria are closely related to each other, we need to compare virtually all nucleotides with each other. This is painstaking work and can only be done with high-throughput methods such as NGS,” said Willmann. In addition, the researchers also have to take into account the patients’ social contacts and their contact with their physical environment. “This helps us assess whether the pathogen was transmitted through human contact or through contact with an environmental constituent. We use this information to find ways to protect other people from being infected with the pathogen under investigation.”

Explaining the spread of pathogens based on genomic data and environmental analyses

3D matrix showing the relationships between Pseudomonas aeruginosa strains. Each strain is represented by a dot. The closer the strains are related to each other, the smaller the distance between them. The matrix shows four groups of strains in four different colours. © Willmann, Tübingen University Hospital

Willmann’s team simulated a multiyear clinical outbreak of highly resistant Pseudomonas strains in order to study the expansion of the pathogen. Although P. aeruginosa is found almost everywhere, it rarely affects healthy people. However, it causes serious infections in people with weakened immune systems which is why it is a major threat to hospital patients who have weakened defences. P. aeruginosa can lead to numerous infections, including urinary tract infections and life-threatening blood poisoning. Willmann and his team have developed a new analysis algorithm that they use to simulate the spread of the bacteria. “Our mortality studies show that it is extremely important to recognise epidemiological situations quickly and at an early stage and our new algorithm helps us to do just this. A patient infected with a strain resistant to most common antibiotics can then be given a suitable reserve antibiotic to prevent the dangerous multiresistant bacteria from spreading to other people,” said Willmann who put his enthusiasm for programming to good use in the development of the algorithm. In 2015, Willmann’s team received the Rudolf Schülke Foundation Hygiene Award for their epidemiological work on the molecular level. In the same year, Willmann also received a DGHM Research Award for his epidemiological research on P. aeruginosa.

In early 2016, Willmann was promoted to the junior professorship “Nosocomial Bacterial Infectious Pathogens” in Tübingen and also finished his training as a medical specialist in microbiology, virology and infection epidemiology. In addition to teaching at the University of Tübingen where he runs the environmental medicine course, Willmann is now working on his habilitation (ed. note: a habilitation is the highest academic qualification in many European and non-European countries and requires the candidate to prove his/her academic ability with numerous peer-reviewed papers, thesis and defence (viva voce). Full university faculty positions in these countries usually require habilitation.). Willmann does not really need a habilitation for the junior professorship, but is happy to kill two birds with one stone, satisfying his inquiring mind and using his research as a basis for a habilitation. Willmann’s current research focuses on elucidating the relationship between the bacterial species involved, the resistance mechanisms, virulence factors and the patient's clinical picture. He wants to find out how resistance and virulence factors influence mortality and whether they are risk factors for the clinical results. These investigations also aim to elucidate and understand the big picture.

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