Oncological patients undergoing stem cell transplantation (allo-SCT) or chemotherapy are often subject to infectious problems. In addition to bacteria, viral and fungal pathogens are particularly frequent causes of life-threatening infections in severely immunocompromised children. Early and reliable diagnosis is an essential prerequisite for successful therapy.
The importance of research and diagnostics
Research, development, and diagnostics in the field of microbiology and myeloid leukemias are the major areas of activity in the St Anna CCRI Molecular Microbiology division, which was established in 1989. The exploitation of diagnostic assays emanating from our work and the performance of specific developmental tasks were transferred to Labdia Labordiagnostik, a non-profit institution established in 2006 as a subsidiary of the St. Anna CCRI.
A patent for molecular detection assays
We have developed and, in part, patented quantitative molecular detection assays for many pathogenic viruses and clinically relevant fungal species. We were able to demonstrate that the clinical implementation of various methods developed in our division permits early assessment of impending infectious complications and provides a basis for optimized diagnostics.
These new diagnostic approaches will contribute to improved treatment strategies against life-threatening infections in severely immunocompromised patients. Moreover, we have studied the patterns of persistence and reactivation of adenoviruses and developed the basis for novel diagnostic and therapeutic strategies for invasive infections which can lead to very severe diseases, particularly in children undergoing allo-SCT.
Further reading: Kneidinger et al. Antiviral Res 2012; Ibrisimovic et al. Antiviral Res 2012 und J Gene Med 2012; Lion T.Clin Microbiol Rev. 2014, 27(3):441-62; Bellutti et al. J Virol. 2015, 89(3):1608-27; Kosulin et al. Clin Microbiol Infect. 2016, 22(4):381.e1-381.e8; Kosulin et al. J Clin Virol. 2016, 80:60-1; Kosulin et al. J Clin Virol. 2016,85:31-36; Kosulin et al. EBioMedicine. 2018 Feb;28:114-119; Landlinger et al. Leukemia 2010; Lion et al. Leukemia 2010; Czurda et al. J Clin Microbiol. 2016, 54(1):148-52; Czurda et al. Methods Mol Biol. 2017;1508:257-266; Nogueira et al. J Microbiol Modern Tech 2017; 2(1): 10; Hiwarkar et al. Rev Med Virol 2018, 28:e1980; Kosulin et al. Front Microbiol 2018, 9:2956; Kosulin et al. Front Microbiol 2019, 10:414; Lion. FEBS Lett 2019, 593: 3571-82; Obrova et al. Am J Hematol 2021, 96: 719-26; Obrova et al. Front Bioeng Biotechnol 2022, 10: 815393; Lion et al. Fields Virology 2022, 129-171.
Targeted diagnostics after allo-SCT
An additional focus of our activities is the development of targeted diagnostics in patients after allo-SCT. A European project coordinated by our center has led to the establishment of a standardized methodology for quantitative analysis of patient- and donor-derived cells (chimerism) (Lion et al. Leukemia 2012). The patented technique was exploited to establish a commercially available diagnostic kit. Moreover, we have established diagnostic approaches facilitating early prediction of graft rejection and other complications which will permit timely therapeutic interventions.
Further reading: Breuer et al. Leukemia 2012; Preuner et al. Methods Mol Biol. 2014;1109:271-91; Preuner et al. Haematologica. 2016 Jun;101(6):741-6; Fortschegger et al. Biol Blood Marrow Transplant 2020, 26: 1218.24;
Complexity of infections
More recently, we have started studying the interactions between bacteria and fungi, in order to better understand the complexity of infections in immunocompromised patients, and to pave the way for improved diagnostics and treatment. We have demonstrated that the important bacterial pathogen Klebsiella peumoniae inhibits the growth of various fungi. The inhibition is reversible, and fungal growth is re-established upon eliminating the bacteria. This observation is of clinical importance because in such instances antibacterial treatment may rapidly unleash fungal growth requiring timely identification and treatment. This example illustrates the potential impact of bacterial-fungal interactions, which represent an essential component of processes occurring within the human microbiome and emphasizes the need for the identification of novel pertinent biomarkers.
Further reading:: Nogueira et al. Sci Rep 2018, 9:218; Nogueira et al. Microorganisms 2019, 7:459;
Clinical implementation of molecular techniques
Our development and clinical implementation of molecular techniques for the surveillance of mutant, therapy-resistant subclones in patients with chronic myeloid leukemia (CML) provided important information on clonal development of the disease, timely detection of resistance, and clone-specific responses to treatment. The new insights facilitated ensuing research aimed at improving our understanding of the pathogenesis of this type of leukemia within a long-term project (Special Research Area Program-SFB) funded by the Austrian Science Fund. The results emanating from this work provided important information on the principles of resistance and improved diagnostic approaches in CML and other types of leukemia.
Further reading: Preuner et al. Leukemia 2008; Preuner et al. EJC 2012; Preuner et al. Int J Mol Sci. 2016, 29;17(5):E642; Kastner et al. Eur J Cancer. 2014, 50(4):793-800; Preuner et al. J Mol Diagn. 2014, 16(4):459-66; Byrgazov K et al. Oncotarget. 2016, 22;7(47):78083-78094; Byrgazov K et al. Leukemia. 2017 Jan;31(1):237-240; Byrgazov K et al. Haematologica. 2018 Jan;103(1):e10-e12); Gleixner et al. Leuk Res 2019, 9:2018; Schneeweis-Gleixner et al. EBiomedicine 2019, 50:111-21. Soverini et al. J Hematol Oncol 2019, 12:39; Popitsch et al. Bioinformatics 2021, 16:526; Schneeweis-Gleixner et al. Am J Canc Res 2021, 11:4470-84.
Projects and funding
Characterization of bacterial-fungal interactions: a basis for discovery of microbial biomarkers (BacFun)
CCRI responsible Principal Investigator: Thomas Lion
Grant from the Austrian Science Fund (FWF), Stand-Alone Project, ID – P 34152
Duration: 01/08/2021 to 31/07/2024
Cold atmospheric plasma for viral decontamination
CCRI responsible Principal Investigator: Thomas Lion
Grant from the Austrian Science Fund (FWF), CEUS Bilateral Joint Projects, ID – I 5293
Duration: 01/04/2021 to 31/03/2024
Lion T. (2019) Adenovirus persistence, reactivation, and clinical management. FEBS Lett. 2019 Dec;593(24):3571-3582. Epub 2019 Sep 8. doi: 10.1002/1873-3468.13576.
Soverini S, Bassan R, Lion T. (2019) Treatment and monitoring of Philadelphia chromosome-positive leukemia patients: recent advances and remaining challenges. J Hematol Oncol. 2019 Apr 23;12(1):39. doi: 10.1186/s13045-019-0729-2.
Nogueira F, Sharghi S, Kuchler K, Lion T. (2019) Pathogenetic Impact of Bacterial-Fungal Interactions. Microorganisms. 2019 Oct 16;7(10):459. doi: 10.3390/microorganisms7100459.
Popitsch N, Preuner S, Lion T. (2021) Nanopanel2 calls phased low-frequency variants in Nanopore panel sequencing data. Bioinformatics. 2021 Jul 16;btab526. doi: 10.1093/bioinformatics/btab526.
Obrová K, Grumaz S, Remely M, Czurda S, Krickl I, Herndlhofer S, Gleixner KV, Sperr WR, Größlinger L, Frank T, Andrade N, Egger-Matiqi T, Peters C, Engstler G, Dworzak M, Attarbaschi A, van Grotel M, van den Heuvel-Eibrink MM, Moiseev IS, Rogacheva Y, Zubarovskaya L, Zubarovskaya N, Pichler H, Lawitschka A, Koller E, Keil F, Valent P, Sohn K, Lion T. (2021) Presence of viremia during febrile neutropenic episodes in patients undergoing chemotherapy for malignant neoplasms. Am J Hematol. 2021 Jun 1;96(6):719-726. doi: 10.1002/ajh.26177.
About Thomas Lion
Univ.-Prof. DDr. Thomas Lion (MD, PhD), MSc, obtained his medical degree from the University of Vienna, a PhD in Genetics from the University of Prague, and a MSc in Social Sciences from the University of Vienna. He is a professor at the Medical University of Vienna and head of the Division for Molecular Microbiology at the Children’s Cancer Research Institute, Austria, and serves as chairman of the Scientific Board of the Austrian Society of Paediatrics. As a certified specialist in paediatric haemato-oncology and medical and chemical laboratory diagnostics, he serves as the Medical Director and CEO of LabDia Labordiagnostik, a centre developing new diagnostic tools and offering molecular diagnostics in the fields of microbiology and leukaemia. He has published about 200 papers in peer-reviewed journals and book chapters, and served as editor of scientific text books. He has been section editor and editorial board member of various journals. He has received 20 national and international research awards and owns different patents on molecular diagnostic techniques.