Redox Biology of Trypanosomes

By means of a multidisciplinary approach, we study the biochemical, structural and biological features that distinguish several key components of the redox system from pathogenic trypanosomatids, parasites that are causative agents of severe diseases in animals and humans (Chagas disease, Leishmaniasis and African sleeping sickness).

These studies allow us to identify and understand the role these components play in parasite biology (e.g. growth, infection, and pathogenesis).

Our research aims to gain understanding into the redox biology of trypanosomatids to guide novel strategies and the development of the safer and more efficacious drugs against this disease.

Members

Marcelo Comini, PhD

Marcelo Comini, PhD

Head

Andrea Medeiros, PhD

Andrea Medeiros, PhD

Associate researcher

Faculty of Medicine, Udelar
amedeiros@pasteur.edu.uy

Mariana Bonilla, PhD

Mariana Bonilla, PhD

Associate researcher

Diego Benítez, PhD

Diego Benítez, PhD

Research assistant

Postdoctoral student
dbenitez@pasteur.edu.uy

Estefanía Dibello, PhD

Estefanía Dibello, PhD

Honorary research associate

Faculty of Chemistry, Udelar
edibello@pasteur.edu.uy

Franca Lorenzelli, Clin. Biochem.

Franca Lorenzelli, Clin. Biochem.

Master's degree student

María Victoria Gutiérrez

María Victoria Gutiérrez

Degree intern

Natalia Oddone, PhD

Natalia Oddone, PhD

Research assistant

Cristina Quiroga, Msc

Cristina Quiroga, Msc

Research assistant

Doctoral student
cquiroga@pasteur.edu.uy

Santiago Ruatta, PhD

Santiago Ruatta, PhD

Honorary postdoctoral researcher

Juan Manuel Mesa, BSc

Juan Manuel Mesa, BSc

Master's degree student

Feriannys Rivas, MSc

Feriannys Rivas, MSc

Doctoral student

Research lines

Fundamental aspects of trypanothione metabolism: synthesis, reduction and utilization
We study the biochemical, structural and biological features that distinguish several key components of the trypanothione system from pathogenic trypanosomatids. Using animal infection models, we investigate the role these molecules play in parasite biology and pathogenesis. The data from these studies allows to validate new drug target candidates, their inhibitors as well as to guide novel drug development strategies.

Development of biosensors for non-invasive and high-content studies
Our laboratory is interested in the development of different types of biosensors (fluorescence- and luminescence-based) that allow the real time and non-invasive monitoring of parasite proliferation, redox state and major signaling pathways. The transgenic cell lines expressing the biosensors allow us to study the role played by the oxidative stress and redox signaling in a variety of cellular processes (e.g. host-pathogen interaction, cell differentiation, cell cycle, apoptosis and metabolic dysfunction). The reporter cell lines are also used in phenotypic drug-screening campaigns and to investigate drug mode of action.

Early phase drug discovery projects
We apply target- and phenotypic-based approaches to screen synthetic and natural compounds that affect, in a selective manner, the growth of the infective form of different trypanosomatid species.
Drug repurposing is also an active area of research in our lab. Drug mode of action at cellular and enzymatic level is addressed to foster and guide drug optimization. Our laboratory relies on an important network of local and international groups working on (medicinal) chemistry to fulfill this goal.

Courses

  • “Redox Chemistry and Biology of Thiols”-III International Theoretical and Practical Course. February 18-28, 2019. Institut Pasteur Montevideo, Uruguay.
  • “International Course: Clinical Flow Cytometry”, October 1-5, 2018, Montevideo, Uruguay.
  • “VII International Course on Trypanosomatid Molecular”, Nov26-Dec1°, 2018, Montevideo, Uruguay.
  • “Theoretical and practical course on lab animals”, March 13-21, 2017, Montevideo, Uruguay.
  • “Cell and Animal Models for Drug Discovery” October 16-27, 2017, Montevideo, Uruguay.
  • “Integrating IP Montevideo technologies”, September 8, 2017, Montevideo, Uruguay.

Projects

2019-2021 – Synthesis and study of new bensoisothiazolone derivatives as multitarget trypanosomatid agents. CSIC I+D 2018. Role: co-responsible.

2019-2021 – MULTI-TARGET QUINONES FOR THE DEVELOPMENT OF TRYPANOSOMIDAL DRUGS. CSIC I+D 2018. Role: collaborator.

2019-2021 – Inference and Comparison of Kinetic and Evolutionary Models of Proteasome Catalytic Cores. CSIC I+D 2018. Role: collaborator.

2019-2021 – Generation of extracts rich in polyphenols from grape pomace. Alliance for Innovation- Technological Development Modality. ANII ALI_2_2018_1_149574. Role: collaborator.

2018-2020 – “Structure-based design of chemical compounds against human pathogen parasites from the Trypanosomatida Order”. Deutsche Forschungsgemeinschaft (DFG or German research Agency) 2018-2020, 352,050 €. Role: collaborator.

2016-2019 – Design and production of new variants of the follicle stimulating hormone (FSH) for its use in species of productive interest. Alliance for Innovation- Technological Development Modality, ANII. $U 640.000 ALI_1_2015_1_5084. Role: collaborator.

2015-2018 – Design of novel biosensors for simultaneous monitoring of redox and cAMP signalling: from the computer to the cell and back to the computer. Fondo María Viña, ANII, FMV_1_2014_1_104000, $U 1.300.000. Role: collaborator.

2015-2017 – The thioredoxin-fold diversity in trypanosomatids and tapeworms. Project ICGEB CRP/URU 14-01–, 2015-2017, € 45000. Role: co-responsible.

2015-2017 – Target-based drug discovery of compounds interfering with trypanothione biosynthesis in trypanosomatids. ACIP Grant – Project A-17-2015. € 70,000. Role: responsible.

2014-2016 – Trypanosoma´s prostaglandin metabolism: role in infection, pathogenesis and drug resistance”, Fiocruz-Pasteur Grant, € 18,000. Role: responsible.

Main publications

vacio
2022
  • Barreiro-Costa O, Quiroga Lozano C, Muñoz E, Rojas-Silva P, Medeiros A, Comini MA, Heredia-Moya J (2022) Evaluation of the anti-Leishmania mexicana and -Trypanosoma brucei activity, and mode of action of 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol). Biomedicines, 1760532.
  • Benítez D, Franco J, Sardi F, Leyva A, Durán R, Choi G, Yang G, Kim T, Kim N, Heo J, Kim K, Lee H, Choi I, Radu C, Shum D, No JH, Comini MA (2022) Drug-like molecules with anti-trypanothione synthetase activity identified by high throughput screening. J Enzyme Inhib Med Chem, 37(1):912-929.
  • Perelmuter K, Tiscornia I, Comini MA, Bollati-Fogolín M (2022) Generation and Characterization of Stable Redox-Reporter Mammalian Cell Lines of Biotechnological Relevance. Sensors, 22(4):1324.
  • Pazos M, Dibello E, Mesa JM, Sames D, Comini MA, Seoane G, Carrera I (2022) Iboga Inspired N-Indolylethyl-Substituted Isoquinuclidines as a Bioactive Scaffold: Chemoenzymatic Synthesis and Characterization as GDNF Releasers and Antitrypanosoma Agents. Molecules, 27(3):829.
  • Dibello E.; Comini M.A., Benítez D (2022) A simple, robust and affordable bioluminescent assay for drug screening against infective African trypanosomes. Methods Mol Biol, 2524: 149-162.
  • Benítez, D.; Medeiros, A.; Quiroga, C.; Comini, M.A.. (2022) A simple bioluminescent assay for the screening of cyto-toxic molecules against the intracellular form of Leishmania infantum. Methods Mol Biol, 2524: 127-147.
  • Benítez D, Dibello E, Bonilla M, Comini MA. (2020) A simple, robust, and affordable bioluminescent assay for drug discovery against infective African trypanosomes. Drug Dev Res, 83: 253-263.
  • Comini MA (2022) Polyamine-based thiols in pathogens. In: Redox Chemistry and Biology of Thiols, Ed. Alvarez B, Comini MA, Salinas G, Trujillo M. Academic Press. Chapter 24: 555-584. ISBN 9780323902199.
  • Ortíz, C., Ruatta, S., Comini, M. (2022). Introduction to Target Validation. In: Scotti, M.T., Bellera, C.L. (eds) Drug Target Selection and Validation. Computer-Aided Drug Discovery and Design, vol 1. Springer, Cham. Chapter 4: 61-82. ISBN: 978-3-030-95894-7.
  • Alvarez B, Comini MA, Salinas G, Trujillo M (2022) Redox Chemistry and Biology of Thiols: 1st Edition. Academic Press. ISBN: 9780323902199
2021
  • Specker G, Piacenza L, Radi R, Comini MA (2021) Thiol-Disulphide Redox Signalling/Control during the Life Cycle of Pathogenic Trypanosomatids. In: Redox regulation of differentiation and de-differentiation, Ed. Berndt C and Lillig CH, CRC Press, Taylor & Francis Group, Chapter 3: 37-55 eBook ISBN 9781003204091.
  • Prolo C, Estrada D, Piacenza, L, Benítez D, Comini, MA, Radi R, Álvarez MN (2021) NOX2-derived superoxide radical is crucial to control acute Trypanosoma cruzi infection. Redox Biology, 2021 46: 102085 DOI: 10.1016/j.redox.2021.10208.
  • Alice JI, Bellera CL, Benítez D, Comini MA, Duchowicz PR, Talevi A (2021) Ensemble learning application to discover new trypanothione synthetase inhibitors. Mol Divers. 2021 25: 1361-1373 DOI: 10.1007/s11030-021-10265-9.
  • Bellera CL, Llanos M, Gantner ME, Rodriguez S, Gavernet L, Comini M, Talevi A (2021) Can drug repurposing strategies be the solution to the COVID-19 crisis? Expert Opin Drug Discov. 16(6):605-612 DOI: 10.1080/17460441.2021.1863943.
  • Klein F, Sardi F, Machado MR, Ortega C, Comini MA, Pantano S (2021) CUTie2: The Attack of the Cyclic Nucleotide Sensor Clones. Front Mol Biosci. 8:629773 DOI: 10.3389/fmolb.2021.629773.
  • Rivas F, Medeiros A, Quiroga C, Benítez D, Comini M, Rodríguez-Arce E, Machado I, Cerecetto H, Gambino D (2021) New Pd-Fe ferrocenyl antiparasitic compounds with bioactive 8-hydroxyquinoline ligands: a comparative study with their Pt-Fe analogues. Dalton Trans. 50(5):1651-1665 DOI: 10.1039/d0dt03963b.
  • Ortíz C, Moraca F, Laverriere M, Jordan A, Hamilton N, Comini MA (2021) Glucose 6-Phosphate Dehydrogenase from Trypanosomes: Selectivity for Steroids and Chemical Validation in Bloodstream Trypanosoma brucei. Molecules 26(2):358 DOI: 10.3390/molecules26020358.
  • Niborski LL, Potenza M, Chirivi RGS, Simonetti L, Ossowski MS, Grippo V, May M, Staquicini DI, Parodi-Talice A, Robello C, Comini MA, Alonso GD, Raats JMH, Gómez KA. Recombinant antibody against Trypanosoma cruzi from patients with chronic Chagas heart disease recognizes mammalian nervous system. EBioMedicine 63:103206 DOI: 10.1016/j.ebiom.2020.103206.
2020
  • Medeiros A, Benítez D, Korn RS, Ferreira VC, Barrera E, Carrión F, Pritsch O, Pantano S, Kunick C, de Oliveira CI, Orban OCF, Comini MA (2020) Mechanistic and biological characterisation of novel N5-substituted paullones targeting the biosynthesis of trypanothione in Leishmania. J Enzyme Inhib Med Chem. 35(1):1345-1358 DOI: 10.1080/14756366.2020.1780227.
  • Benitez D, Comini MA, Anusevičius Ž, Šarlauskas J, Miliukienė V, Miliuvienė E, Čėnas N (2020). Chemija 31(2), 111-117 DOI: 10.6001/chemija.v31i2.4223.
  • Parakh S, Shadfar S, Perri ER, Ragagnin AMG, Piattoni CV, Fogolín MB, Yuan KC, Shahheydari H, Don EK, Thomas CJ, Hong Y, Comini MA, Laird AS, Spencer DM, Atkin JD (2020). The Redox Activity of Protein Disulfide Isomerase Inhibits ALS Phenotypes in Cellular and Zebrafish Models. iScience 23(5):101097 DOI: 10.1016/j.isci.2020.101097.
  • Franco J, Scarone L, Comini MA (2020) Novel distamycin analogues that block the cell cycle of African trypanosomes with high selectivity and potency. Eur J Med Chem. 189: 112043. DOI: 10.1016/j.ejmech.2020.112043.
2019
  • Talevi A, Carrillo C, Comini MA (2019) The thiol-polyamine metabolism of Trypanosoma cruzi: molecular targets and drug repurposing strategies. Curr. Med. Chem. 26: 1-20 DOI: 10.2174/0929867325666180926151059.
  • Currier RB, Ulrich K, Leroux AE, Dirdjaja N, Deambrosi M, Bonilla M, Ahmed YL, Adrian L, Antelmann H, Jakob U, Comini MA, Krauth-Siegel RL (2019) An essential thioredoxin-type protein of Trypanosoma brucei acts as redox-regulated mitochondrial chaperone. PLoS Pathog. 15(9):e1008065.
  • Rivas F, Medeiros A, Comini M, Suescun L, Rodríguez Arce E, Martins M, Pinheiro T, Marques F, Gambino D (2019) Pt-Fe ferrocenyl compounds with hydroxyquinoline ligands show selective cytotoxicity on highly proliferative cells. J Inorg Biochem. 199:110779.
  • Vairoletti F, Medeiros A, Fontán P, Meléndrez J, Tabárez C, Salinas G, Franco J, Comini MA, Saldaña J, Jancik V, Mahler G, Saiz C (2019) Synthesis of bicyclic 1,4-thiazepines as novel anti-Trypanosoma brucei brucei agents. Med Chem Comm. 10: 1481-1487.
  • Rodríguez Arce E, Putzu E, Lapier M, Maya JD, Olea Azar C, Echeverría GA, Piro OE, Medeiros A, Sardi F, Comini M, Risi G, Salinas G, Correia I, Pessoa JC, Otero L, Gambino D. New heterobimetallic ferrocenyl derivatives are promising antitrypanosomal agents. Dalton Trans. 2019 May 3. doi: 10.1039/c9dt01317b. [Epub ahead of print] PubMed PMID: 31049548.
  • Ortíz C, Botti H, Buschiazzo A, Comini MA (2019) Glucose-6-Phosphate Dehydrogenasefrom the Human Pathogen Trypanosoma cruzi Evolved Unique Structural Features toSupport Efficient Product Formation. J Mol Biol. 431(11): 2143-2162
  • Ferrer MJ, Wehrendt DP, Bonilla M, Comini MA, Tellez-Iñón MT, Potenza M (2019) Production of recombinant Trypanosoma cruzi antigens in Leishmania tarentolae. Methods Mol. Biol. 1955: 105-118.
  • Piattoni CV, Sardi F, Klein F, Pantano S, Bollati-Fogolin M, Comini MA. (2019) New red-shifted fluorescent biosensor for monitoring intracellular redox changes. Free Radic Biol Med. 134:545-554.
  • Manta B, Möller MN, Bonilla M, Deambrosi M, Grunberg K, Bellanda M, Comini MA, Ferrer-Sueta G (2019) The key role of a redox- active glutaredoxin in the evolution of the thiol-redox metabolism of trypanosomatid parasites revealed by kinetics. J. Biol. Chem. 294: 3235-3248.
  • Mesías AC, Sasoni N, Arias DG, Pérez Brandán C, Orban OCF, Kunick C, Robello C, Comini MA, Garg NJ, Zago MP (2019) Trypanothione synthetase confers growth, survival advantage and resistance to anti-protozoal drugs in Trypanosoma cruzi. Free Radic Biol Med. 130: 23-34.
2018
  • Talevi A, Carrillo C, Comini MA (2018) The thiol-polyamine metabolism of Trypanosoma cruzi: molecular targets and drug repurposing strategies. Curr. Med. Chem. 26: 1-20.
  • Sturlese M, Manta B, Bertarello A, Bonilla M, Lelli M, Zambelli B, Grunberg K, Mammi S, Comini M, Bellanda M (2018) Monothiol glutaredoxin 1 from trypanosomes contains a lineage-specific, intrinsically disordered, regulatory region. Sci. Rep. 8: 13716
  • Rivas F, Medeiros A, Rodríguez Arce E, Comini MA, Ribeiro CM, Pavan FR, Gambino D (2018) New heterobimetallic ferrocenyl derivatives: evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium tuberculosis. J. Inorg. Biochem. 187: 73-84.
  • Ebersoll S, Musunda B, Schmenger T, Dirdjaja N, Bonilla M, Manta B, Comini MA, Krauth-Siegel RL (2018) A glutaredoxin in the mitochondrial intermembrane space has stage-specific functions in the thermo-tolerance and proliferation of African trypanosomes. Redox Biology 15: 532-547.
  • Salinas G, Comini MA (2018) Alternative thiol-based redox systems. Antioxid Redox Signal. 28: 407-409.
  • Manta B, Bonilla M, Fiestas L, Sturlese M, Salinas G, Bellanda M, Comini MA. (2018) Polyamine-based thiols in Trypanosomatids: evolution, protein structural adaptations and biological functions. Antioxid Redox Signal. 28: 463-486.
  • Franco J, Scarone L, Comini MA (2018) Drugs and drug resistance in African and American trypanosomiasis. In: Annual Reports in Medicinal Chemistry: Medicinal Chemistry Approaches To Overcome Antibiotic Resistance volume 51, Ed. Botta, M., Academic Press, Elsevier, Chapter 3: 97-133.
  • Comini MA (2018) Biosynthesis of Polyamine–Glutathione Derivatives in Enterobacteria and Kinetoplastida. In: Glutathione, Ed. Flohé, L., CRC Press: Boca Raton, pp. 285-305.
2017
  • Franco J, Sardi F, Szilágyi L, Kövér K, Fehér K, Comini MA (2017) Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes. Int. J. Parasitol. Drugs & Drug Resist. 7: 303-313.
  • Ornithine decarboxylase or gamma-glutamylcysteine synthetase overexpression protects Leishmania (Vianna) guyanensis against antimony (2017) Fonseca MS, Comini M, Resende BV, Santi AMM, Zoboli AP, Moreira DS, Monte-Neto RL and Murta SMF. Exp. Parasitol. 175: 36-43.
  • Franco J, Medeiros A, Benítez D, Perelmuter K, Serra G, Comini MA, Scarone L (2017) In vitro activity and mode of action of Distamycin analogues against African trypanosomes. Eu. J. Med. Chem. 126: 776-788.
2016
  • Orban OCF, Korn RS, Benítez D, Medeiros A, Preu L, Loaëc N, Meijer L, Koch O, Comini MA, and Kunick C (2016) 5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms. Bioorg Med Chem. 24(16):3790-800.
  • Benítez D, Medeiros A, Fiestas L, Panozzo-Zenere EA, Maiwald F, Prousis KC, Roussaki M, Calogeropoulou T, Detsi A, Jaeger T, Šarlauskas J, Peterlin Mašič L, Kunick C, Labadie GR, Flohé L, Comini MA. (2016) Identification of Novel Chemical Scaffolds Inhibiting Trypanothione Synthetase from Pathogenic Trypanosomatids. PLoS Negl Trop Dis. 10(4): e0004617. http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004617
  • Ortiz C, Moraca F, Medeiros A, Botta M, Hamilton N, Comini M. (2016) Binding Mode and Selectivity of Steroids towards Glucose-6-phosphate Dehydrogenase from the Pathogen Trypanosoma cruzi. Molecules 21(3), 368; http://www.mdpi.com/1420-3049/21/3/368.
  • Bonilla M, Krull E, Irigoín F, Salinas G, Comini MA. (2016) Selenoproteins of African trypanosomes are dispensable for parasite survival in an animal host. Mol Biochem Parasitol. 206(1-2): 13-19.
  • Alberca LN, Sbaraglini ML, Balcazar D, Fraccaroli L, Carrillo C, Medeiros A, Benitez D, Comini M, Talevi A. (2016) Discovery of novel polyamine analogs with anti-protozoal activity by computer guided drug repositioning. J Comput Aided Mol Des. 30(4): 305-321.
  • Comini MA (2016) Measurement and meaning of cellular thiol:disufhide redox status. Free Radic Res. 50(2): 246-71.
  • Randall L, Manta B, Nelson KJ, Santos J, Poole LB, Denicola A. (2016) Structural changes upon peroxynitrite-mediated nitration of peroxiredoxin 2; nitrated Prx2 resembles its disulfide-oxidized form. Arch Biochem Biophys. 590: 101-108.
2015
  • Musunda B, Benítez D, Dirdjaja N, Comini MA, Krauth-Siegel RL. (2015) Glutaredoxin-deficiency confers bloodstream Trypanosoma brucei with improved thermotolerance. Mol Biochem Parasitol. 204(2): 93-105.
  • Bisio H, Bonilla M, Manta B, Graña M, Salzman V, Aguilar PS, Gladyshev VN, Comini MA, Salinas G. (2015) A New Class of Thioredoxin-Related Protein Able to Bind Iron-Sulfur Clusters. Antioxid Redox Signal. Oct 27. [Epub ahead of print] PubMed PMID: 26381228.
  • Stefani M, Sturlese M, Manta B, Löhr F, Mammi S, Comini M, Bellanda M (2015) (1)H, (13)C and (15)N resonance assignment of the cytosolic dithiol glutaredoxin 1 from the pathogen Trypanosoma brucei. Biomol NMR Assign. 10(1): 85-88.
  • Rodríguez Arce E, Sarniguet C, Moraes TS, Vieites M, Tomaz AI, Medeiros A, Comini MA, Varela J, Cerecetto H, González M, Marques F, García MH, Otero L, Gambino D (2015) A new ruthenium cyclopentadienyl azole compound with activity on tumor cell lines and trypanosomatid parasites. J Coord. Chem. 1-15.
  • Fernández M, Arce ER, Sarniguet C, Morais TS, Tomaz AI, Azar CO, Figueroa R, Diego Maya J, Medeiros A, Comini M, Helena Garcia M, Otero L, Gambino D. (2015) Novel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasites. J Inorg Biochem. 153: 306-314.
  • Miserachs HG, Cipriani M, Grau J, Vilaseca M, Lorenzo J, Medeiros A, Comini MA, Gambino D, Otero L, Moreno V. (2015) Antitumor and antiparasitic activity of novel ruthenium compounds with polycyclic aromatic ligands. J Inorg Biochem. 150: 38-47.
2014
  • Peña S., Fagundez C., Medeiros A., Comini M.A., Scarone L., Sellanes D., Manta E., Tulla-Puche J., Albericio F., Stewart L., Yardley V. and Serra G. (2014) Synthesis of Cyclohexapeptides as Promising Antimalarial and Anti-trypanosomal Agents. Med. Chem. Comm. 3: 1443-1448.
  • Sousa A.F., Gomes-Alves A.G., Benítez D., Comini M.A., Flohé L., Jaeger T., Passos J., Stuhlmann F., Tomás A. M., Castro H. (2014) Genetic and chemical analyses reveal that trypanothione synthetase but not glutathionylspermidine synthetase is essential for Leishmania infantum. Free Rad. Biol. Med. 73: 229-238.
  • Maiwald F; Benítez D; Charquero D; Abad Dar M; Erdmann H; Preu L;Koch O; Hoscher C; Meijer L; Comini MA; Kunick C (2014) 9- and 11-substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma.. Eu. J. Med. Chem. 83: 274-283.
  • Randall LM, Manta B, Hugo M, Gil M, Batthyàny C, Trujillo M, Poole LB, Denicola A (2014) Nitration transforms a sensitive peroxiredoxin 2 into a more active and robust peroxidase. J Biol Chem. 289(22): 15536-43.
  • Sturlese M, Lelli M, Manta B, Mammi S, Comini MA, Bellanda M. (2014) (1)H, (13)C and (15)N resonance assignment of the mature form of monothiol glutaredoxin 1 from the pathogen Trypanosoma brucei. Biomol NMR Assign 9: 143-146.
  • Hiller C., Nissen A., Benitez D., Comini M., Krauth-Siegel R. L (2014) Cytosolic Peroxidases Protect the Lysosome of Bloodstream African Trypanosomes from Iron-Mediated Membrane Damage. PLoS Pathogens 10(4):e1004075.
2013
  • Manta B., Pavan C., Sturlese M., Medeiros A., Crispo M., Berndt C., Krauth-Siegel R.L., Bellanda M. and Comini M.A. (2013) Iron-sulfur cluster binding by mitochondrial monothiol glutaredoxin-1 of Trypanosoma brucei: molecular basis of iron-sulfur cluster coordination and relevance for parasite infectivity. Antioxid. Redox Signal. 19(7):665-82
  • Sardi F, Manta B, Portillo-Ledesma S, Knoops B, Comini MA, Ferrer-Sueta G. 2013. Determination of acidity and nucleophilicity in thiols by reaction with monobromobimane and fluorescence detection. Anal Biochem. 435(1):74-82.
  • Manta B, Comini M, Medeiros A, Hugo M, Trujillo M, Radi R. 2013. Trypanothione: A unique bis-glutathionyl derivative in trypanosomatids. Biochim Biophys Acta. 1830(5):3199-216.
  • Fernández M., Becco L., Correia I., Benítez J., Piro O.E., Echeverria G.A., Medeiros A., Comini M., Lavaggi M.L., González M., Cerecetto H., Moreno V., Pessoa J.C., Garat B. and Gambino D. (2013) Oxidovanadium(IV) and dioxidovanadium(V) complexes of tridentate salicylaldehyde semicarbazones: Searching for prospective antitrypanosomal agents. J. Inorg Biochem. 127:150-60.
  • Comini M.A., Krauth-Siegel R.L., Bellanda M. (2013) Mono- and di-thiol glutaredoxins in the trypanothione-based redox metabolism of pathogenic trypanosomes. Antiox. Redox Signal. 19(7):708-22.
  • Comini M.A, Ortiz C., Cazzulo, J.J. (2013). Drug Targets in Trypanosomal and Leishmanial Pentose Phosphate Pathway. In: Trypanosomatids diseases, molecular routes to drug discovery. Ed. T. Jäger, O. Koch, L.Flohé, Wiley-Blackwell. ISBN: 978-3-527-33255-7.
  • Comini M.A., Flohé L. (2013). The trypanothione-based redox metabolism of trypanosomatids. In: Trypanosomatids diseases, molecular routes to drug discovery. Ed. T. Jäger, O. Koch, L.Flohé, Wiley-Blackwell ISBN: 978-3-527-33255-7.
2012
  • Peña S., Scarone L., Medeiros A., Manta E., Comini M., Serra G. 2012. Synthesis of precursors and macrocycle analogs of aerucyclamides as anti-trypanosomal agents. Med. Chem. Commun. 3(11):1443-1448
  • Demoro B., Sarniguet C., Sánchez-Delgado R., Rossi M., Liebowitz D., Caruso, F., Olea-Azar C., Moreno V., Medeiros A., Comini M.A., Otero L., Gambino D. 2012New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents. Dalton Transactions. 41(5):1534-43.
  • Manta B., Fleitas A.L., Comini M.A. (2012). Iron Metabolism in Pathogenic Trypanosomes. In: Iron Metabolism. Ed. S.Arora, InTech Press. ISBN 979-953-307-162-5.
  • Comini M.A., Medeiros A., Manta B. (2012). Stress response in the infective stage of Trypanosoma brucei. In: Stress Response in Microbiology. Ed. J.M. Requena, Horizon Scientific Press. ISBN 978-1-908230-04-1.
2011
  • Ortiz C., Larrieux N., Medeiros A., Botti H., Comini M., Buschiazzo, A. 2011. Expression, crystallization and preliminary X-ray crystallographic analysis of glucose-6-phosphate dehydrogenase from the human pathogen Trypanosoma cruzi in complex with substrate. Acta Crystallogr Sect F Struct Biol Cryst Commun. 67(Pt 11):1457-61 / 67(Pt 12):1674
  • Roldan A., Comini M.A., Crispo M., Krauth-Siegel R.L. (2011) Lipoamide dehydrogenase is essential for both bloodstream and procyclic Trypanosoma brucei. Mol. Microbiol. 81(3):623-39
  • Manta B., Obal G., Ricciardi A., Pritsch O., Denicola A. (2011) Tools to evaluate conformation in protein products. 2011. Biotechnology Journal 6(6):731-41.
  • Ferrer-Sueta G., Manta B., Botti H., Radi R., Trujillo M., Denicola A. 2011. Factors affecting protein thiol reactivity and specificity in peroxide reduction. Chem. Res. Tox. 24(4):434-50.
2009
  • Comini M.A., Dirdjaja N., Kaschel M., Krauth-Siegel R.L., 2009. Preparative enzymatic synthesis of trypanothione and trypanothione analogues. Int. J. Parasitol. 39, 1059-1062.
2008
  • Comini M.A., Rettig J., Dirdjaja N., Hanschmann E.M., Berndt C., Krauth-Siegel R.L., 2008. Monothiol Glutaredoxin-1 Is an Essential Iron-Sulfur Protein in the Mitochondrion of African Trypanosomes. J Biol. Chem. 283, 27785-27798.
  • Irigoín F., Cibils L., Comini M.A., Wilkinson S.R., Flohé L., Radi R., 2008. Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification. Free Radic. Biol. Med. 45, 733-742.
  • Buchholz K., Comini M.A., Wissenbach D., Schirmer R. H., Krauth-Siegel R. L. and Gromer S. (2008) Cytotoxic interactions of methylene blue with trypanosomatids-specific disulfide reductases and their dithiol products. Mol. Biochem. Parasitol., 160: 65-69.
  • Krauth-Siegel R. L. and Comini M.A. (2008) Redox control in trypanosomatids, parasitic protozoa with trypanothione-based thiol metabolism. Biochem. Biophys. Acta, 1780: 1236-1248.
  • Filser M., Comini M.A., Dirdjaja N., Molina-Navarro M., Herrero E., and Krauth-Siegel R. L. (2008) Cloning, functional analysis and localization of monothiol glutaredoxin-1 from Trypanosoma brucei. Biol. Chem., 389: 21-32.
  • Bollati-Fogolín M. and Comini M. A. (2008). Chapter 3: Clonagem e Expressão de Proteínas Heterólogas em Células Animais, pp. 40-76. In: Tecnologia do Cultivo de Células Animais: de Biofármacos a Terapia Gênica. Eds. Ângela Maria Moraes Elisabeth F. P. Augusto e Leda Dos Reis Castilho. Editora Roca, São Paulo, Brazil.
2007
  • Schlecker T., Comini M.A., Melchers J., Ruppert T., and Krauth-Siegel R. L. (2007) Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of Trypanosoma brucei. Biochem. J., 405: 445-454.
  • Xolalpa W., Vallecillo A., Lara M., Spallek R., Comini M., Singh M., and Espitia C. (2007) Identification of novel bacterial plasminogen-binding proteins in the human pathogen Mycobacterium tuberculosis. Proteomics, 7: 3332-3341.
  • Comini M.A., Krauth-Siegel R.L., and Flohé, L. (2007) Depletion of the thioredoxin homologue tryparedoxin impairs anti-oxidative defense in African trypanosomes. Biochem. J., 402: 43-49.
  • Bollati-Fogolín M. and Comini M. A. (2007). Chapter 3: Cloning and Expression of Heterologous Proteins in Animal Cells, pp. 39-73. In: Animal Cell Technology: From Biopharmaceuticals to Gene Therapy. Eds. Leda R. Castilho, Ângela Maria Moraes, Elisabeth F. P. Augusto and Michael Butler. Taylor & Francis, New York, US and Abingdon, UK.
  • Schlecker T., Comini M. A., and Krauth-Siegel R. L. (2007) . Chapter 11: The trypanothione system, pp. 231-252. In: Peroxiredoxin systems: Structures and functions. Eds. Leopold Flohé and Robin J. Harris. Springer-Verlag, Berlin, Germany.
2006
  • Trujillo M., Mauri P., Benazzi L., Comini M.A., De Palma A., Flohé L., Radi R., Stehr M., Singh M., Ursini F. and Jäger T. (2006) The mycobacterial thioredoxin peroxidase can act as a one-cysteine-peroxiredoxin. J. Biol. Chem., 281: 20555-20566.
2005
  • Comini M.A., Menge U., Wissing J. and Flohé L. (2005) Trypanothione synthesis in Crithidia revisited. J. Biol. Chem., 280: 6850-6860.
  • Comini M.A., Menge U., and Flohé L. (2005) “Convenient isolation and kinetic mechanism of glutathionylspermidine synthetase from Crithidia fasciculata. Vol. 272 (1997) 11908–11915″. J. Biol. Chem., 280: 7407.
2004
  • Comini M.A., Guerrero S. A., Haile S., Menge U., Lünsdorf H. and Flohé L. (2004) Validation of Trypanosoma brucei trypanothione synthetase as drug target. Free Radic. Biol. Med., 36: 1289-1302.
  • Imaz S. M., Comini M.A., Zerbini E., Sequeira M. D., Latini O., Claus J. D. and Singh M. (2004) Evaluation of commercial ELISA kits for the detection of Tuberculosis in Argentinean population. J. Clin. Microbiol., 42: 884-887.
2003
  • Comini M.A., Menge U. and Flohé L. (2003) Biosynthesis of trypanothione in Trypanosoma brucei brucei. Biol. Chem., 384: 653-656.
2001
  • Imaz M. S., Comini M.A., Zerbini E., Sequeira M. D., Spoletti M. J., Etchart A. A., Pagano H. J., Bonifasich E., Díaz N., Claus J. D. and Singh M. (2001) Evaluation of the diagnostic value of measuring IgG, IgM and IgA antibodies to the recombinant 16-kilodalton antigen of Mycobacterium tuberculosis in childhood tuberculosis. Int. J. Tuberc. Lung Dis., 5 (11): 1036-1043.