Publications
2026
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Avidin is evolutionarily conserved in fish but dispensable for development and resistance against Streptococcus agalactiae in zebrafish
Biotin is a vital cofactor in cellular carboxylation reactions and avidins are biotin-binding proteins that are produced by bacteria and fungi but also by egg-laying vertebrates, including avian species and zebrafish (Danio rerio). Although avidins have proposed roles in embryonic development and immunity, their biological significance is poorly characterized. Moreover, besides zebrafish, the presence of avidins in other fish species has not been explored. Here, we cataloged avidins in fish... -
Structural insights into multitargeting <em>Mycobacterium tuberculosis</em> Pkn kinases
Tuberculosis remains one of the leading major global health challenges, driven by the emergence of multidrug-resistant and extensively drug-resistant bacterial strains. Resistant strains complicate treatment, which often requires prolonged use of toxic second- and third-line drugs. Protein phosphorylation plays critical roles in Mycobacterium tuberculosis, with serine/threonine kinases PknA, PknB, and PknG being essential for survival, virulence, and persistence. In this study, we screened an... -
First-in-class nonsteroidal anti-inflammatory drug and carbonic anhydrase inhibitor hybrid compounds as effective antimycobacterial agents
We investigated the in vitro effects of nonsteroidal anti-inflammatory drug-carbonic anhydrase inhibitor hybrids (NSAID-CAIs) on β-carbonic anhydrases 1-3 expressed by Mycobacterium tuberculosis, as well as their antimycobacterial efficacy in a zebrafish infection model. The primary aims were to investigate whether these enzymes represent valid therapeutic targets and whether NSAID-CAIs constitute potential drug candidates for tuberculosis. In vitro inhibition activity against the carbonic...
2025
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Oral microbiome diversity and composition before and after chemotherapy treatment in pediatric oncology patients
CONCLUSIONS: These findings indicate that chemotherapy-induced microbiome shifts associate with OM risk, highlighting the potential for microbial markers to predict high-risk patients and support protective strategies. -
M.marinum lacking epsH shows increased biofilm formation in vitro and boosted antibiotic tolerance in zebrafish
Recent discoveries have indicated that biofilm communities may play a role in natural drug tolerance of Mycobacterium tuberculosis. A transposon-based mutation library of a closely related species, Mycobacterium marinum, was used to identify clones in which the relative amount of extracellular DNA (eDNA), an important component of the extracellular matrix of biofilms, is altered. The disruption of a putative glycosyl transferase gene QDR78 11175, epsH, caused a substantial increase of the eDNA...
2024
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Revised whole genome and DNA methylome of <em>Mycobacterium marinum</em> type strain ATCC 927<sup>T</sup>
Mycobacterium marinum, a slow-growing Actinobacterium, typically induces tuberculosis-like disease in fish. Here, we report a new reference sequence for M. marinum ATCC 927^(T), along with its DNA methylome. This aims to maximize the research potential of this type strain and facilitates investigations into the pathomechanisms of human tuberculosis.
2023
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Generation of a Zebrafish Knock-In Model Recapitulating Childhood ETV6::RUNX1-Positive B-Cell Precursor Acute Lymphoblastic Leukemia
Approximately 25% of children with B-cell precursor acute lymphoblastic leukemia (pB-ALL) harbor the t(12;21)(p13;q22) translocation, leading to the ETV6::RUNX1 (E::R) fusion gene. This translocation occurs in utero, but the disease is much less common than the prevalence of the fusion in newborns, suggesting that secondary mutations are required for overt leukemia. The role of these secondary mutations remains unclear and may contribute to treatment resistance and disease recurrence. We... -
<em>In vitro</em> and <em>ex vivo</em> proteomics of <em>Mycobacterium marinum</em> biofilms and the development of biofilm-binding synthetic nanobodies
The antibiotic-tolerant biofilms present in tuberculous granulomas add an additional layer of complexity when treating mycobacterial infections, including tuberculosis (TB). For a more efficient treatment of TB, the biofilm forms of mycobacteria warrant specific attention. Here, we used Mycobacterium marinum (Mmr) as a biofilm-forming model to identify the abundant proteins covering the biofilm surface. We used biotinylation/streptavidin-based proteomics on the proteins exposed at the Mmr... -
Characterization of the innate immune response to Streptococcus pneumoniae infection in zebrafish
Streptococcus pneumoniae (pneumococcus) is one of the most frequent causes of pneumonia, sepsis and meningitis in humans, and an important cause of mortality among children and the elderly. We have previously reported the suitability of the zebrafish (Danio rerio) larval model for the study of the host-pathogen interactions in pneumococcal infection. In the present study, we characterized the zebrafish innate immune response to pneumococcus in detail through a whole-genome level transcriptome...
2022
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Food-Grade Bacteria Combat Pathogens by Blocking AHL-Mediated Quorum Sensing and Biofilm Formation
Disrupting bacterial quorum sensing (QS) signaling is a promising strategy to combat pathogenic biofilms without the development of antibiotic resistance. Here, we report that food-associated bacteria can interfere with the biofilm formation of a Gram-negative pathogenic bacterium by targeting its AHL (acyl-homoserine lactone) QS system. This was demonstrated by screening metabolic end-products of different lactobacilli and propionibacteria using Gram-negative and biofilm-forming Chromobacterium...
2021
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Surface-Shaving Proteomics of Mycobacterium marinum Identifies Biofilm Subtype-Specific Changes Affecting Virulence, Tolerance, and Persistence
The complex cell wall and biofilm matrix (ECM) act as key barriers to antibiotics in mycobacteria. Here, the ECM and envelope proteins of Mycobacterium marinum ATCC 927, a nontuberculous mycobacterial model, were monitored over 3 months by label-free proteomics and compared with cell surface proteins on planktonic cells to uncover pathways leading to virulence, tolerance, and persistence. We show that ATCC 927 forms pellicle-type and submerged-type biofilms (PBFs and SBFs, respectively) after 2...
2020
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SIX6 is a TAL1-regulated transcription factor in T-ALL and associated with inferior outcome
T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy driven by abnormal activity of transcription factors. Here we report an aberrant expression of the developmental transcription factor SIX6 in the TAL1-subtype of T-ALL. Our results demonstrate that the binding of TAL1 and GATA3 transcription factors into an upstream enhancer element directly regulates SIX6 expression. High expression of SIX6 was associated with inferior event-free survival within three independent patient... -
Randomized controlled and double-blinded study of Caphosol versus saline oral rinses in pediatric patients with cancer
CONCLUSIONS: No difference in prevention of oral mucositis was observed between the use of Caphosol or saline rinses. -
<em>In vitro</em> inhibition of <em>Mycobacterium tuberculosis β</em>-carbonic anhydrase 3 with Mono- and dithiocarbamates and evaluation of their toxicity using zebrafish developing embryos
We investigated a panel of 14 compounds belonging to the monothiocarbamate (MTC) and dithiocarbamate (DTC) series against the β-carbonic anhydrase 3 (β-CA3) of Mycobacterium tuberculosis (Mtb). We also evaluated all compounds for toxicity using 1-5-day post fertilisation zebrafish embryos. 11 out of the 14 investigated derivatives showed effective nanomolar or submicromolar in vitro inhibition against the β-CA3 (K(I)s 2.4-812.0 nM), and among them four DTCs of the series (8-10 and 12) showed... -
Characterization of immune response against Mycobacterium marinum infection in the main hematopoietic organ of adult zebrafish (Danio rerio)
Tuberculosis remains a major global health challenge. To gain information about genes important for defense against tuberculosis, we used a well-established tuberculosis model; Mycobacterium marinum infection in adult zebrafish. To characterize the immunological response to mycobacterial infection at 14 days post infection, we performed a whole-genome level transcriptome analysis using cells from kidney, the main hematopoietic organ of adult zebrafish. Among the upregulated genes, those...
2019
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<em>Mycobacterium tuberculosis</em> <em>β</em>-Carbonic Anhydrases: Novel Targets for Developing Antituberculosis Drugs
The genome of Mycobacterium tuberculosis (Mtb) encodes three β-carbonic anhydrases (CAs, EC 4.2.1.1) that are crucial for the life cycle of the bacterium. The Mtb β-CAs have been cloned and characterized, and the catalytic activities of the enzymes have been studied. The crystal structures of two of the enzymes have been resolved. In vitro inhibition studies have been conducted using different classes of carbonic anhydrase inhibitors (CAIs). In vivo inhibition studies of pathogenic bacteria... -
Characterization of immune response against Mycobacterium marinum infection in the main hematopoietic organ of adult zebrafish (Danio rerio)
Tuberculosis remains a major global health challenge. To gain information about genes important for defense against tuberculosis, we used a well-established tuberculosis model; Mycobacterium marinum infection in adult zebrafish. To characterize the immunological response to mycobacterial infection at 14 days post infection, we performed a whole-genome level transcriptome analysis using cells from kidney, the main hematopoietic organ of adult zebrafish. Among the upregulated genes, those... -
Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
The zebrafish is a widely used vertebrate model organism for the disease and phenotype-based drug discovery. The zebrafish generates many offspring, has transparent embryos and rapid external development. Zebrafish embryos can, therefore, also be used for the rapid evaluation of toxicity of the drugs that are precious and available in small quantities. In the present article, a method for the efficient screening of the toxicity of chemical compounds using 1-5-day post fertilization embryos is... -
PCR-based zebrafish model for personalised medicine in head and neck cancer
CONCLUSION: We introduce a novel, easy, fast and cost-effective PCR-based in vivo zebrafish larvae assay to test the response of cell lines and clinical tumour samples to anti-cancer drugs. This method goes hand-by-hand with the commonly used imaging assay.
2018
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Carbonic Anhydrase Inhibitors as Novel Drugs against Mycobacterial β-Carbonic Anhydrases: An Update on <em>In Vitro</em> and <em>In Vivo</em> Studies
Mycobacteria cause a variety of diseases, such as tuberculosis, leprosy, and opportunistic diseases in immunocompromised people. The treatment of these diseases is problematic, necessitating the development of novel treatment strategies. Recently, β-carbonic anhydrases (β-CAs) have emerged as potential drug targets in mycobacteria. The genomes of mycobacteria encode for three β-CAs that have been cloned and characterized from Mycobacterium tuberculosis (Mtb) and the crystal structures of two of... -
Modeling Tuberculosis in Mycobacterium marinum Infected Adult Zebrafish
Mycobacterium tuberculosis is currently the deadliest human pathogen causing 1.7 million deaths and 10.4 million infections every year. Exposure to this bacterium causes a wide disease spectrum in humans ranging from a sterilized infection to an actively progressing deadly disease. The most common form is the latent tuberculosis, which is asymptomatic, but has the potential to reactivate into a fulminant disease. Adult zebrafish and its natural pathogen Mycobacterium marinum have recently proven... -
Nitroimidazole-based inhibitors DTP338 and DTP348 are safe for zebrafish embryos and efficiently inhibit the activity of human CA IX in Xenopus oocytes
Carbonic anhydrase (CA) IX is a hypoxia inducible enzyme that is highly expressed in solid tumours. Therefore, it has been considered as an anticancer target using specific chemical inhibitors. The nitroimidazoles DTP338 and DTP348 have been shown to inhibit CA IX in nanomolar range in vitro and reduce extracellular acidification in hypoxia, and impair tumour growth. We screened these compounds for toxicity using zebrafish embryos and measured their in vivo effects on human CA IX in Xenopus... -
Identification of protective postexposure mycobacterial vaccine antigens using an immunosuppression-based reactivation model in the zebrafish
Roughly one third of the human population carries a latent Mycobacterium tuberculosis infection, with a 5-10% lifetime risk of reactivation to active tuberculosis and further spreading the disease. The mechanisms leading to the reactivation of a latent Mycobacterium tuberculosis infection are insufficiently understood. Here, we used a natural fish pathogen, Mycobacterium marinum, to model the reactivation of a mycobacterial infection in the adult zebrafish (Danio rerio). A low-dose... -
Priming of innate antimycobacterial immunity by heat-killed <em>Listeria monocytogenes</em> induces sterilizing response in the adult zebrafish tuberculosis model
Mycobacterium tuberculosis remains one of the most problematic infectious agents, owing to its highly developed mechanisms to evade host immune responses combined with the increasing emergence of antibiotic resistance. Host-directed therapies aiming to optimize immune responses to improve bacterial eradication or to limit excessive inflammation are a new strategy for the treatment of tuberculosis. In this study, we have established a zebrafish-Mycobacterium marinum natural host-pathogen model...