Projects Data-driven Clinical Microbiology

Many bacterial infections, particularly those caused by multidrug-resistant organisms such as carbapenemase-producing organisms (CPO) or vancomycin-resistant enterococci (VRE) frequently occur during a hospital stay. These pathogens are resistant to critically important classes of antimicrobial agents, complicating treatment efforts. By linking epidemiological data with whole-genome sequencing analyses of bacteria (genomic epidemiology), we investigate patient-, pathogen-, or environment-specific factors that influence the spread and potential transmission of bacterial pathogens in hospitals.
In our research projects, we employ case-control studies, retrospective cohort studies, and prospective study designs, and we are involved in multicenter studies. In addition to multidrug-resistant organisms such as VRE, our focus is on the Gram-negative Gammaproteobacteriae Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
The findings from our research aim to be utilized, in collaboration with the infection prevention and control team of MHH, to interrupt infection chains through targeted interventions and, in the long term, to enable predictions about the transmissibility of bacteria based on their genetic characteristics.

References:

Böhne, C.‡, Knegendorf, L‡, Schwab, F., Ebadi, E., Bange, F. C., Vital, M., Schlüter, D., Hansen, G., Pirr, S., Peter, C., Bohnhorst, B., & Baier, C. (2022). Epidemiology and infection control of Methicillin-resistant Staphylococcus aureus in a German tertiary neonatal intensive and intermediate care unit: A retrospective study (2013-2020). PloS one, 17(9), e0275087. https://doi.org/10.1371/journal.pone.0275087

Jochim-Vukosavic, A., Schwab, F., Knegendorf, L., Schlüter, D., Bange, F. C., Ebadi, E.‡, & Baier, C.‡ (2024). Epidemiology and infection control of vancomycin-resistant enterococci at a German university hospital: A three-year retrospective cohort study. PloS one, 19(2), e0297866. https://doi.org/10.1371/journal.pone.0297866

Vital, M., Woltemate, S., Schlüter, D., Krezdorn, N., Dieck, T., Dastagir, K., Bange, F. C., Ebadi, E., Vogt, P. M., Knegendorf, L.‡, & Baier, C.‡ (2024). Molecular epidemiology, microbiological features and infection control strategies for carbapenem-resistant Acinetobacter baumannii in a German burn and plastic surgery center (2020-2022). Antimicrobial resistance and infection control, 13(1), 99. https://doi.org/10.1186/s13756-024-01459-5

Funding:

HZI-internal funding „Prevention or integrated data sciences”, project “Breaking the chain of Pseudomonas aeruginosa infection in the hospital (Susanne Häußler)”
 

Antimicrobial resistance poses a significant challenge in the treatment of bacterial infections. To address this challenge, new diagnostically useful insights into the responsible pathogens are essential to enable more specific therapies.
Our goal is to better understand the mechanisms of bacterial regulation and the mutual influence of resistance and virulence determinants. Through molecular characterization of the bacteria, we aim to investigate the emergence of “pathotypes”, regardless of their resistance. For this purpose, we employ whole genome sequencing using both short-read (Illumina) and long-read (Oxford Nanopore) methods to reconstruct plasmids and determine the precise localization of virulence genes within the genome. For the analysis of pathogenicity, we utilize data from the clinical courses of patients from whom the pathogens were isolated, as well as the model organism Galleria mellonella.
The focus of our research group is on the pathogen Klebsiella pneumoniae, which belongs to the critical group of WHO Bacterial Priority Pathogens. In the context of collaborative projects, we also examine Escherichia coli and Enterococcus faecium. The results of our research are intended to ultimately facilitate the development of better therapeutic regimens for bacterial infections based on whole genome sequencing, contributing significantly to the optimization of diagnostics.

References:

Klein, F.‡, Wellhöner F.‡, Freise, A.‡, Niculovic, K. M., Junca, H., Vicente, M., Kats, E., Dos Anjos Borges, L. G., Knegendorf, L

., Cirksena, K., Woelfl, F., Abdullah, H. F., Schulz, M., Plumeier, I., Kahl, S., Albers, I., Zoodsma, M., Vital, M., Voigtländer, T., Lenzen, H., Schmitz, J., Saborowski, A., Manns, M. P., Solbach, P., Bräsen J. H., Gerold, G., Xu, C. J., Wedemeyer, H., Münster-Kühnel, A. K., Pieper, D. H., & Heidrich, B. (2024). Cholangiocyte glycocalyx degradation boosts primary sclerosing cholangitis. MedRxiv (Preprint). doi.org/10.1101/2024.06.27.24309484 

Funding:

University-internal performance fund MHH („Hochschulinterne Leistungsförderung“ HiLF I) 2023, project ”Correlation of Klebsiella sp. pathogenicity with circulating virulence plasmids and resistance to tellurite”