Dr. Maksym Kitsera
Scientific Summary & Publication Record
Scientific Summary
During his doctoral studies at the University of Graz, Dr. Kitsera's research centered on the opportunistic pathogen Klebsiella oxytoca and its enterotoxins, tilimycin and tilivalline. His foundational work established that these two secondary metabolites possess distinct molecular mechanisms: tilimycin acts as a DNA-alkylating genotoxin, while tilivalline functions as a microtubule stabilizer, collectively driving the pathogenesis of antibiotic-associated hemorrhagic colitis (Unterhauser et al., 2019). To facilitate these in vivo and in vitro studies, he contributed to the development of highly sensitive HPLC-HR-ESMS2 analytical methods utilizing 15N-labeled internal standards to simultaneously quantify these toxins in complex biological matrices (Glabonjat et al., 2021).
Subsequent investigations into the physiological impact of these toxins demonstrated that tilimycin accumulation leads to severe apoptotic erosion of the intestinal epithelium and colonic stem cell mutations, highlighting its capacity to drive somatic genetic changes in the host (Pöltl et al., 2023). Crucially, the research revealed that transient tilimycin synthesis in the murine gut acts as a pro-mutagenic antibiotic; it not only antagonizes niche competitors and destabilizes the microbiota but also accelerates the de novo acquisition of antibiotic resistance in co-resident pathogens (Kienesberger et al., 2022).
Following his PhD, his postdoctoral tenure at the Bernhard Nocht Institute for Tropical Medicine (BNITM) transitioned to virology within S3/S4 high-containment environments. Here, his work focused on evaluating and optimizing humanized mouse models for infectious diseases. This included comprehensive analyses of recent advancements in NSG and NRG humanized mouse models for viral and immune research (Kitsera et al., 2023), as well as specific evaluations of Hu-PBL mice for studying the pathogenesis of human-restricted viruses (Brunetti et al., 2023).
Publications
- Brunetti, J. E., Kitsera, M., Muñoz-Fontela, C., & Rodríguez, E. (2023). Use of Hu-PBL Mice to Study Pathogenesis of Human-Restricted Viruses. Viruses, 15(1), 228. https://doi.org/10.3390/v15010228
- Glabonjat, R. A., Kitsera, M., Unterhauser, K., Lembacher-Fadum, C., Högenauer, C., Raber, G., Breinbauer, R., & Zechner, E. L. (2021). Simultaneous quantification of enterotoxins tilimycin and tilivalline in biological matrices using HPLC high resolution ESMS2 based on isotopically 15N-labeled internal standards. Talanta, 222, 121677. https://doi.org/10.1016/j.talanta.2020.121677
- Kienesberger, S., Cosic, A., Kitsera, M., Raffl, S., Hiesinger, M., Leitner, E., Halwachs, B., Gorkiewicz, G., Glabonjat, R. A., Raber, G., Lembacher-Fadum, C., Breinbauer, R., Schild, S., & Zechner, E. L. (2022). Enterotoxin tilimycin from gut-resident Klebsiella promotes mutational evolution and antibiotic resistance in mice. Nature Microbiology, 7, 1834-1848. https://doi.org/10.1038/s41564-022-01260-3
- Kitsera, M., Brunetti, J. E., & Rodríguez, E. (2023). Recent Developments in NSG and NRG Humanized Mouse Models for Their Use in Viral and Immune Research. Viruses, 15(2), 478. https://doi.org/10.3390/v15020478
- Pöltl, L., Kitsera, M., Raffl, S., Schild, S., Cosic, A., Kienesberger, S., Unterhauser, K., Raber, G., Lembacher-Fadum, C., Breinbauer, R., Gorkiewicz, G., Sebastian, C., Hoefler, G., & Zechner, E. L. (2023). Microbiota-derived genotoxin tilimycin generates colonic stem cell mutations. Cell Reports, 42(3), 112199. https://doi.org/10.1016/j.celrep.2023.112199
- Unterhauser, K., Pöltl, L., Schneditz, G., Kienesberger, S., Glabonjat, R. A., Kitsera, M., Pletz, J., Josa-Prado, F., Dornisch, E., Lembacher-Fadum, C., Roier, S., Gorkiewicz, G., Lucena, D., Barasoain, I., Kroutil, W., Wiedner, M., Loizou, J. I., Breinbauer, R., Díaz, J. F., Schild, S., Högenauer, C., & Zechner, E. L. (2019). Klebsiella oxytoca enterotoxins tilimycin and tilivalline have distinct host DNA-damaging and microtubule-stabilizing activities. Proceedings of the National Academy of Sciences, 116(9), 3774-3783. https://doi.org/10.1073/pnas.1819154116