Biometals and Drug Discovery Lab

Biometals and Drug Discovery Lab

RNDr. Róbert Šuťák, Ph.D.

RNDr. Róbert Šuťák, Ph.D. — Project head

The Faculty of Science of the Charles University

About us

Our laboratory is focused on 2 topics:

1) Characterization of nutrition requirements, uptake mechanisms and intracellular metabolism of metals, especially iron, and copper, and identification of the molecules involved in these processes. 

2) Repurposing of existing drugs and discovery of new drugs against medically important pathogenic eukaryotic microorganisms.

 

Biometals

The importance of metals for the survival of microorganisms is best demonstrated on iron. Phytoplankton contributes to nearly 50% of the primary production, yet waters of the oceans contain limiting concentrations of several essential nutrients, especially iron, an element that is required in particular abundance by photosynthetic organisms. Iron also plays an important role in host-pathogen relationship. Many pathogens are highly dependent on a sufficient supply of iron and take up this metal by multiple and divergent pathways from the host. The activation and expression of such microbial iron acquisition systems is linked to their pathogenicity and proliferation. Thus the withholding of iron is an effective antimicrobial defence strategy of the host. Our project is focused on the characterization of nutrition requirements, mechanism of uptake and intracellular metabolism of metals, mainly iron and copper and identification of molecules involved in these processes. Research includes metabolism specific for pathogenic organisms (parasitic protists) and strategies necessary for life in nutritionally limited environment (unicellular algae). As a model organism we are using Saccharomyces cerevisiae.

Representation of iron transport systems in parasitic protists.
Jan Mach & Robert Sutak. Metallomics 2020,12, 1335-1347
© The Royal Society of Chemistry 2020

 

Drug discovery

Many of the currently available anti-parasitic and anti-fungal frontline drugs have severe limitations, including adverse side effects, complex administration, and increasing occurrence of resistance. Our laboratory is involved in discovering new and repurposing drugs against medically important pathogenic eukaryotic microorganisms such as the causative agents of sleeping sickness, Chagas disease, malaria, the pathogenic yeasts Candida albicans and Cryptococcus neoformans, the brain-eating amoeba Naegleria fowleri, and the causative agent of acanthamoebic keratitis. For in vivo studies, we use mouse models of Cryptococcus neoformans and Trypanosoma brucei infection. An example of successful drug repurposing is the potential use of the anticancer drug MitoTam as a highly selective antiparasitic.

 

Schematic representation of the proposed MitoTam mode of action on T. brucei mitochondrion

 

Group webpage

News

Publications

2023

Ženíšková K, Mach J, Arbon D, Štursa J, Werner L, Zoltner M, Sutak R. The 4-Aminomethylphenoxy-Benzoxaborole AN3057 as a Potential Treatment Option for Primary Amoebic Meningoencephalitis. Antimicrob Agents Chemother. 2023

2022

Arbon D, Ženíšková K, Šubrtová K, Mach J, Štursa J, Machado M, Zahedifard F, Leštinová T, Hierro-Yap C, Neuzil J, Volf P, Ganter M, Zoltner M, Zíková A, Werner L, Sutak R. Repurposing of MitoTam: Novel Anti-Cancer Drug Candidate Exhibits Potent Activity against Major Protozoan and Fungal Pathogens. Antimicrob Agents Chemother. 2022 Aug 16;66(8):e0072722. doi: 10.1128/aac.00727-22. Epub 2022 Jul 20. PMID: 35856666; PMCID: PMC9380531.

Maria Grechnikova, Dominik Arbon, Kateřina Ženíšková, Ronald Malych, Jan Mach, Lucie Krejbichová, Aneta Šimáčková, Robert Sutak,
Elucidation of iron homeostasis in Acanthamoeba castellanii, International Journal for Parasitology, Volume 52, Issue 8, 2022, Pages 497-508, ISSN 0020-7519,
https://doi.org/10.1016/j.ijpara.2022.03.007.

Ženíšková K, Grechnikova M and Sutak R (2022) Copper Metabolism in Naegleria gruberi and Its Deadly Relative Naegleria fowleri. Front. Cell Dev. Biol. 10:853463. doi: 10.3389/fcell.2022.853463

Ronald Malych, Zoltán Füssy, Kateřina Ženíšková, Dominik Arbon, Vladimír Hampl, Ivan Hrdý, Robert Sutak, The response of Naegleria gruberi to oxidative stress, Metallomics, Volume 14, Issue 3, March 2022, mfac009, https://doi.org/10.1093/mtomcs/mfac009

Malych R., Stopka P., Mach J., Kotabová E., Prášil O., Sutak R. Flow cytometry-based study of model marine microalgal consortia revealed an ecological advantage of siderophore utilization by the dinoflagellate Amphidinium carterae. Comput Struct Biotechnol J. 2022

2021

Kotabova E, Malych R, Pierella Karlusich JJ, Kazamia E, Eichner M, Mach J, Lesuisse E, Bowler C, Prášil O, Sutak R. Complex Response of the Chlorarachniophyte Bigelowiella natans to Iron Availability. mSystems. 2021 Feb 9;6(1):e00738-20. doi: 10.1128/mSystems.00738-20. PMID: 33563784; PMCID: PMC7883536.

2020

Grechnikova M., Ženíšková K., Malych R., Mach J., Sutak R. Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system. Int J Parasitol Drugs Drug Resist. 2020

Mach J., Sutak R. Iron in parasitic protists - from uptake to storage and where we can interfere. Metallomics. 2020.

2018

Kazamia E, Sutak R, Paz-Yepes J, Dorrell RG, Vieira FRJ, Mach J, Morrissey J, Leon S, Lam F, Pelletier E, Camadro JM, Bowler C, Lesuisse E. Endocytosismediated siderophore uptake as a strategy for Fe acquisition in diatoms. Sci Adv. 2018

Mach J, Bíla J, Ženíšková K, Arbon D, Malych R, Glavanakovová M, Nývltová E, Sutak R. Iron economy in Naegleria gruberi reflects its metabolic flexibility. Int J Parasitol. 2018

2012

Sutak R, Hrdy I, Dolezal P, Cabala R, Sedinová M, Lewin J, Harant K, Müller M, Tachezy J. Secondary alcohol dehydrogenase catalyzes the reduction of exogenous acetone to 2-propanol in Trichomonas vaginalis. FEBS J. 2012

Sutak R, Botebol H, Blaiseau PL, Léger T, Bouget FY, Camadro JM, Lesuisse E. A comparative study of iron uptake mechanisms in marine microalgae: iron binding at the cell surface is a critical step. Plant Physiol. 2012

2010

Sutak R, Slapeta J, San Roman M, Camadro JM, Lesuisse E. Nonreductive iron uptake mechanism in the marine alveolate Chromera velia. Plant Physiol. 2010

Sutak R, Slapeta J, San R M, Camadro J M and Lesuisse E (2010) Nonreductive Iron Uptake Mechanism in the Marine Alveolate Chromera Velia. Plant Physiol 154:991-1000.

2008

Sutak R, Lesuisse E, Tachezy J and Richardson D R (2008) Crusade for Iron: Iron Uptake in Unicellular Eukaryotes and Its Significance for Virulence. Trends Microbiol 16:261-268.