BacFun

Diagnostics and treatment of bacterial and fungal infections pose a major challenge in pediatric and adult patients with impaired immunity, including particularly patients with cancer and recipients of organ or bone marrow transplantation. Owing to the lack of rapid and reliable diagnostics, treatment of infections often relies on prophylactic or experience-based approaches. Bacteria and fungi occupy the same locations in the human body and aggregate to form so-called biofilms within which they can communicate either in mutually supportive or competitive ways. Communication can occur via production of proteins and secretion of small molecules. The interaction between bacteria and fungi in biofilms can result in increased resistance to antibiotic and antifungal treatment, and can render the microbes capable of evading the immune system. Our recent studies showed that certain bacteria can prevent fungal growth, but upon elimination of the bacteria by antibiotics, the fungi can grow and expand again. Studying how bacteria and fungi interact is therefore of major relevance for appropriate diagnostics and treatment. In the present project, we intend to i) characterize molecular interactions between the pathogens Candida and Klebsiella representative of specific niches in the human host, ii) identify small molecules governing the Candida-Klebsiella interaction as potential biomarkers and iii) characterize the host immune response to polymicrobial infections by Candida and Klebsiella. To pursue the indicated tasks, we will use laboratory techniques already established at our center to investigate how these microbes communicate, and how they evade the immune system. The indicated studies involving the analysis of specific genes, proteins and small molecules are expected to provide the experimental basis for the identification and exploitation of diagnostically useful biomarkers for bacterial-fungal infections. Improved understanding of the complex interactions between microbes affecting their biological properties will ultimately contribute to more efficient management of life- threatening invasive infections in high-risk patients.