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Nele Wellinghausen - the fascination of pathogens

Nele Wellinghausen has always been interested in plants and animals. As a teenager she studied ferns and won the German "Jugend forscht" competition. Nowadays, the medical expert carries out research on microorganisms, specifically on pathogens that lead to sepsis. She has just commenced a clinical trial with 500 patients, in which Wellinghausen hopes to find ways that enable the more rapid diagnosis of sepsis.

The 37-year-old is dealing with sepsis, a disease that experts refer to as “a largely unknown killer” which leads to the death of more than 100,000 people in Germany every year. Sepsis is the number three cause of death in Germany, with a mortality rate of approximately 40 per cent.

The danger is lurking in hospitals

Prof. Nele Wellinghausen is hoping to speed up the diagnosis of sepsis (Photo: Pytlik)
The number of sepsis cases is growing; doubling in the last few years, said Wellinghausen. The danger of falling sick of sepsis is – ironically - highest in hospitals. This is the paradox: Although the (intensive) treatment of patients is constantly being improved, the risk of infection is nevertheless increasing. Immunocompromised patients, tumour patients, patients after surgical operations involving catheters, syringes, cannulas and other equipment, are at greatest risk because these tools are perfect gateways into the body. Moreover, many bacteria become resistant to antibiotics, leading to an increase in mortality.

Sepsis is very common but difficult to diagnose and recognize clinically. Up to four days can pass before the pathogen can be identified in the blood. For this reason, and because laboratory diagnostics can only identify one in five pathogens, patients suspected of suffering from sepsis, are treated with a broad-spectrum antibiotic.

Bad hit rate in blood cultures

Blood is withdrawn and cultured for subsequent pathogen identification. This takes a long time and is not successful in most cases. (Photo: Wellinghausen)
Blood is withdrawn and cultured for subsequent pathogen identification. This takes a long time and is not successful in most cases. (Photo: Wellinghausen)
According to Wellinghausen, this bad hit rate can have several reasons: the bacteria are no longer viable when transferring the blood into the test vial, the patient has already been treated with antibiotics or the defence cells have already broken down the microbes, leaving behind fragments that cannot be detected in blood culture.

In vivo instead of in vitro

Bottles for blood samples. (Photo: University Hospital Ulm)
Dr. Wellinghausen tried to change this situation using molecular-biological methods (real-time PCR): Her goal was to use PCR to directly identify microorganisms in blood culture bottles. As a result of this work, Wellinghausen’s team has developed several methods that are suitable to identify 95 per cent of the sepsis pathogens within four hours. Moreover, the universal PCR assay differentiates Gram-positive from Gram-negative bacteria, an advantage for the treatment of the patient, as the treatment can subsequently be adapted more specifically.

In December 2007, a clinical study was started at the University Hospital in Ulm which involves 500 patients (adults and children) suspected of suffering from sepsis. Wellinghausen hopes that the study will confirm the suitability of the rapid molecular-biological test. If the test proves suitable, Wellinghausen’s industrial partner will start to commercialise a test set. The assay will be used by big microbiological laboratories for patients with severe sepsis and compete with two further rapid test methods.

Rapid identification has many advantages

A streak of bacteria on blood agar in a petri dish. One can see gray colonies.
Aeromonas hydrophila, on blood agar – a much-feared hospital pathogen. (Photo: Wellinghausen)
For Wellinghausen, the advantages of the rapid test are clear: if the pathogen is known, then the doctor can adjust the therapy to the pathogen rather than using a broad-spectrum antibiotic; long-term resistances and the spread of multiresistant pathogens are thus prevented. In addition, costs are saved. As good as PCR assays might be, bacterial antibiotic resistance can only be tested with blood cultures. The molecular identification does not indicate the resistance of the bacteria. In such cases, medical diagnostics still rely on the determination of the bacteria’s phenotype since the genome of many bacteria is still unknown.

Why is sepsis diagnostics so underdeveloped? Wellinghausen is sure that this is mainly due to the fact that blood is not suitable for modern molecular-biological identification methods. Blood contains many substances that might impair methods such as PCR. “It is often the case that blood culture diagnostics – as primitive as it might be – is more effective than all modern technologies.”

Interested in the broad disease picture

Staphylococcus aureus – this bacterial species lives on human skin, but can also mutate into a sepsis pathogen. (Photo: T. Pietzcker)
During her studies, Wellinghausen became fascinated by pathogens, how they infect the human body and make it sick. Wellinghausen soon realized that the most exciting thing about microbiology was the “broad disease pictures that affect the entire body.” She is very interested in biological issues and enjoys the microbiological work in the laboratory, the detective-like search for, and identification of, these microbes. Moreover, the field of microbiology is very dynamic – every year new pathogens are discovered.

Wellinghausen was the first to discover an Inquilinus limosis bacterium in a cystic fibrosis patient in Germany and also found that this pathogen was the cause of the chronic infections experienced by cystic fibrosis patients. In the meantime, the identification method has been refined significantly. “This is of particular importance as it helps patients.” Wellinghausen does not see herself as a basic researcher; she needs to work with patients.

Fungi do not only damage trees

This also explains Wellinghausen’s enthusiasm for another discovery which she made together with European and South-African colleagues. The discovery came after months of delicate work. She identified a fungus in an immunocompromised patient that attacks lungs and the brain, thereby leading to a variety of serious diseases. The fungus, Ophiostoma piceae, is a member of a fungus order that also caused the devastating Dutch elm disease.

No master plan

Sepsis pathogen, Staphylococcus aureus, on blood agar. (Photo: Wellinghausen)
Many scientists have an academic master plan which they follow meticulously. Prof. Dr. Nele Wellinghausen is different. She never intended to pursue an academic career. “Many things just happened,” said Wellinghausen telling about her original plan of going to Africa or Central America as tropical disease specialist. Moreover, there were no jobs available in Hamburg where she obtained her degree, which is why she ended up in Ulm. In 1997, she accepted a position in the Infectiology Unit in the Department of Internal Medicine; then she moved on to work in the Department of Microbiology. Wellinghausen enjoyed this very much, as she could work in the laboratory and focus on research while working in the field of infectious diseases.

Work must be fun

At the age of 33, Wellinghausen received her habilitation on the molecular diagnosis of infectious pathogens. She then became a medical specialist and was appointed associate professor in 2005. “This was quicker than I thought,” said Wellinghausen, also mentioning that, despite this speed, she never stayed the night in the laboratory. So, what is the secret of her success? “The most important thing always is that the work must be enjoyable and fascinating, then everything goes smoothly. If one has a number of publications, then everything seems to run smoothly and many more doors seem to open,” says Wellinghausen summarizing the basis of her success.

wp - 31.01.2008
© BIOPRO Baden-Württemberg GmbH
Further information:
Prof. Dr. Nele Wellinghausen
Institut für Med. Mikrobiologie und Hygiene
Universitätsklinikum Ulm
Albert-Einstein-Allee 11
89081 Ulm
Tel.: +49-731-500-65314
Fax: +49-731-500-65302
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/nele-wellinghausen-the-fascination-of-pathogens