Pathogenic Ecophysiology
RG Fließwasser

Research in the Fließwasser Group

The research group “Pathogenic Ecophysiology” investigates the adaptations of resistant, enteropathogenic bacteria (such as vancomycin-resistant enterococci) to the ecological conditions of the human gut microbiome.

Members of the research group analyze how interactions between bacteria and the host, as well as shifts between eubiotic and dysbiotic conditions, promote the colonization and spread of pathogens. Based on these findings, the scientists are developing novel strategies for the selective and efficient decolonization of these bacteria, which can be used as an alternative to or in combination with classical antibiotics.

For this purpose, the research group uses, among other methods, an in vitro gut model to study pathogens within a bacterial community under controlled, colon-like conditions, thereby validating innovative decolonization strategies in preclinical studies.

AG Fliesswasser April 2026_2.webp
© UKB/Rolf Müller

News

Schnelltestentwicklung zur Diagnose schwer behandelbarer VRE-Bakterien
Enterococcus faecium ist ein Bakterium, das von Natur aus gegen viele gängige Antibiotika resistent ist. Insbesondere bei vulnerablen Patientengruppen, wie immungeschwächten Personen, kann das Bakterium schwer behandelbare Infektionen verursachen und stellt daher ein bedeutendes Problem als nosokomialer Infektionserreger dar. Vancomycin-resistente Enterococcus faecium (VRE) zählen zu den besonders besorgniserregenden antibiotikaresistenten Problemkeimen, da ihre Behandlung stark eingeschränkt ist. Die Resistenz beruht auf den Enzymkomplexen VanA oder VanB, die Vancomycin unwirksam machen. VanB wird jedoch in gängigen Empfindlichkeitstests der Diagnostik oft nicht zuverlässig erkannt, was zu ineffektiven Therapien und einer weiteren Ausbreitung von VRE führen kann.
Mögliche Alternative zu Antibiotika aus Bakterien
Viele Bakterien produzieren Substanzen, um sich in ihrer wettbewerbsintensiven natürlichen Umgebung gegenüber Konkurrenten Vorteile zu verschaffen. Forschende des Universitätsklinikums Bonn (UKB), der Universität Bonn und des Deutschen Zentrums für Infektionsforschung (DZIF) haben ein neues so genanntes Lantibiotikum, nämlich das Epilancin A37 gefunden. Es wird von Staphylokokken, die beispielsweise die Haut besiedeln, gebildet und wirkt spezifisch gegen deren dortige Hauptkonkurrenten, die Corynebakterien. Diese Spezifität wird vermutlich über einen ganz besonderen Wirkmechanismus vermittelt, den die Forschenden im Detail entschlüsseln konnten. Ihre Ergebnisse sind jetzt im renommierten ISME Journal veröffentlicht.

Research Focus

The human gut is colonized by thousands of different microbial species that coexist in an antagonistic, mutualistic, or even symbiotic relationship. While coevolution has predominantly led to a commensal and generally beneficial relationship between microbes and their host, under certain conditions, pathogenic bacteria can also establish themselves within the gut microbiota. These disease-causing bacteria are summarized under the term “enteropathogens”.

In most cases, the finely balanced network of microbe-microbe-host interactions ensures that enteropathogens are controlled. However, a dysbiotic event can disrupt this eubiotic balance, allowing pathogens to gain an advantage, displace commensal bacteria, and even cause life-threatening infections. In this context, the ecological factors that play a role and the physiological adaptations pathogens require are poorly understood for many species. Research into these relationships, therefore offers untapped potential for developing new strategies in the fight against bacterial infections, especially in the preventive decolonization of antibiotic-resistant pathogens.  We are currently focusing on the critical group of ESKAPE pathogens and developing highly specific approaches that remove only the pathogenic bacteria without affecting the commensal microorganisms of the gut community. In this way, we are helping to avoid dysbiosis, dangerous infections, and the problematic development of drug resistance under controllable conditions.

In vitro gut community model (ivGCM)

To study enteropathogens within a bacterial community, we use a bioreactor-based in vitro gut model that mimics the conditions of the human gastrointestinal tract and allows us to culture a wide variety of challenging, often strictly anaerobic gut bacteria. In our longitudinal experiments, we primarily evaluate decolonization strategies and microbiome interventions, focusing in particular on their specificity and efficacy against the target pathogen, as well as their effects on the commensal host community. With this system, we can model different sections of the gut, such as the large or small intestine, and simulate both eubiotic and dysbiotic conditions. This flexible model is widely used across our various research areas.

in vitro Darmmodell
Laboraufbau eines in vitro Darmmodells mit zwei kontrollierten Bioreaktoren. © UKB/Johann F. Saba
Verbreitung von Polysulfidtoleranz-Genen in Staphylokokken
Verbreitung von Polysulfidtoleranz-Genen in Staphylokokken © Verena Wiemann

Polysulfide tolerance as a selection factor for pathogens

Inorganic polysulfides are toxic intermediates of sulfide oxidation that can act as an ecological stressor in microbial habitats. Pathogens, including those found in clinical wastewater or on the human intestinal mucosa, also come into contact with these reactive sulfur compounds, especially under dysbiotic conditions. Interestingly, we have found that some antibiotic-resistant pathogens, such as methicillin-resistant Staphylococcus aureus, often exhibit a particularly high tolerance to polysulfides. We are currently investigating exactly how polysulfide tolerance is related to antibiotic resistance and how this ecological stressor affects the spread of pathogens.

Phage decolonization of enteropathogens

Bacteriophages are viruses that specifically infect bacteria and kill the bacteria during their replication cycle. There is a wide diversity of these viruses in all bacterial habitats, and they can also be used medically in the form of phage therapy, where they kill pathogens in a highly selective manner. Due to their specificity, they are particularly useful for the preventive decolonization of pathogenic bacteria, including as an alternative in cases of antibiotic resistance. We are currently searching for clinically useful phages in unusual sources and evaluating phage preparations as promising decolonization agents for resistant enteropathogens.

Phagen infizieren Bakterien spezifisch
© colourbox

Team

Group leader

Avatar Fließwasser

Dr. rer. nat. Thomas Fließwasser

R 0.005

Meckenheimer Allee 168

53115 Bonn

Doctoral Students


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