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Fibronectin degradation as biomarker for Trypanosoma cruzi infection and treatment monitoring in mice

Published online by Cambridge University Press:  24 May 2021

Nora Adriana Hernández-Cuevas Open the ORCID record for Nora Adriana Hernández-Cuevas [Opens in a new window] ,
Andrea Marín-Cervera ,
Shineily Garcia-Polanco ,
Pedro Martínez-Vega Open the ORCID record for Pedro Martínez-Vega [Opens in a new window] ,
Miguel Rosado-Vallado  and
Eric Dumonteil
Nora Adriana Hernández-Cuevas*
Affiliation:
Laboratorio de Parasitología, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Mérida, México
Andrea Marín-Cervera
Affiliation:
Laboratorio de Parasitología, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Mérida, México
Shineily Garcia-Polanco
Affiliation:
Laboratorio de Parasitología, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Mérida, México
Pedro Martínez-Vega
Affiliation:
Laboratorio de Parasitología, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Mérida, México
Miguel Rosado-Vallado
Affiliation:
Laboratorio de Parasitología, Centro de Investigaciones Regionales ‘Dr. Hideyo Noguchi’, Universidad Autónoma de Yucatán, Mérida, México
Eric Dumonteil
Affiliation:
Department of Tropical Medicine, School of Public Health and Tropical Medicine, and Vector-Borne and Infectious Disease Research Center, Tulane University, New Orleans, LA, USA
*
Author for correspondence: Nora Adriana Hernández-Cuevas, E-mail: nora.hernandez@correo.uady.mx
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Abstract

Biomarkers (coming from host or parasite) to monitor Chagas disease (CD) progression as well as the therapeutic response in chronic CD are critically needed, since seronegativization, which may be considered the best indicator of therapeutic cure, takes several years to be observed in adults. Several molecules have been suggested as biomarkers for CD, however, they have to be validated. Taking advantage of mouse models of Trypanosoma cruzi infection, we investigated changes in the degradation profile of fibronectin in plasma. The degradation profile of fibronectin was different in the acute phase compared to the chronic phase of the infection. Fibronectin fragments of approximately 150, 100, 40 and 30 kDa were identified. Furthermore, those degradation profiles correlated with acute parasitaemia as well as with cardiac parasite burden and tissue damage during the infection. The usefulness of fibronectin degradation as a biomarker for therapeutic response following drug treatment and immunotherapeutic vaccination also was evaluated and a decreased fibronectin degradation profile was observed upon benznidazole or a vaccine candidate treatment.

Keywords

Acute and chronic infectionbiomarkerChagas diseasefibronectinmouse modeltreatment
Type
Research Article
Information
Parasitology , Volume 148 , Issue 9 , August 2021 , pp. 1067 - 1073
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle ScholarPubMed
Britto, CC (2009) Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations. Memórias do Instituto Oswaldo Cruz 104, 122–135.CrossRefGoogle ScholarPubMed
Cancado, JR (2002) Long term evaluation of etiological treatment of chagas disease with benznidazole. Revista do Instituto de Medicina Tropical de Sao Paulo 44, 29–37.CrossRefGoogle ScholarPubMed
Clausen, L, Abildgaard, AB, Gersing, SK, Stein, A, Lindorff-Larsen, K and Hartmann-Petersen, R (2019) Chapter two – protein stability and degradation in health and disease. In Donev, R (ed.), Advances in Protein Chemistry and Structural Biology, vol. 114. San Diego, CA: Academic Press, pp. 61–83.Google Scholar
de la Cruz, JJ, Villanueva-Lizama, L, Dzul-Huchim, V, Ramírez-Sierra, M-J, Martinez-Vega, P, Rosado-Vallado, M, Ortega-Lopez, J, Flores-Pucheta, CI, Gillespie, P, Zhan, B, Bottazzi, ME, Hotez, PJ and Dumonteil, E (2018) Production of recombinant TSA-1 and evaluation of its potential for the immuno-therapeutic control of Trypanosoma cruzi infection in mice. Human Vaccines & Immunotherapeutics 15, 210–219.CrossRefGoogle ScholarPubMed
Dumonteil, E, Escobedo-Ortegon, J, Reyes-Rodriguez, N, Arjona-Torres, A and Ramirez-Sierra, MJ (2004) Immunotherapy of Trypanosoma cruzi infection with DNA vaccines in mice. Infection and Immunity 72, 46–53.CrossRefGoogle ScholarPubMed
Dumonteil, E, Bottazzi, ME, Zhan, B, Heffernan, MJ, Jones, K, Valenzuela, JG, Kamhawi, S, Ortega, J, de Leon Rosales, SP, Lee, BY, Bacon, KM, Fleischer, B, Slingsby, BT, Cravioto, MB, Tapia-Conyer, R and Hotez, PJ (2012) Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects. Expert Review of Vaccines 11, 1043–1055.CrossRefGoogle ScholarPubMed
Fares, RCG, Gomes, JDAS, Garzoni, LR, Waghabi, MC, Saraiva, RM, Medeiros, NI, Oliveira-Prado, R, Sangenis, LHC, Chambela, MDC, de Araújo, FF, Teixeira-Carvalho, A, Damásio, MP, Valente, VA, Ferreira, KS, Sousa, GR, Rocha, MODC and Correa-Oliveira, R (2013) Matrix metalloproteinases 2 and 9 are differentially expressed in patients with indeterminate and cardiac clinical forms of Chagas disease. Infection and Immunity 81, 3600–3608.CrossRefGoogle ScholarPubMed
Gironés, N, Carbajosa, S, Guerrero, NA, Poveda, C, Chillón-Marinas, C and Fresno, M (2014) Global metabolomic profiling of acute myocarditis caused by Trypanosoma cruzi infection. PLoS Neglected Tropical Diseases 8, e3337.CrossRefGoogle ScholarPubMed
Granjon, E, Dichtel-Danjoy, M-L, Saba, E, Sabino, E, Campos de Oliveira, L and Zrein, M (2016) Development of a novel multiplex immunoassay multi-cruzi for the serological confirmation of Chagas disease. PLoS Neglected Tropical Diseases 10, e0004596.CrossRefGoogle ScholarPubMed
Jackson, Y, Wyssa, B and Chappuis, F (2020) Tolerance to nifurtimox and benznidazole in adult patients with chronic Chagas’ disease. Journal of Antimicrobial Chemotherapy 75, 690–696.CrossRefGoogle ScholarPubMed
Jelicks, LA and Tanowitz, HB (2011) Advances in imaging of animal models of Chagas disease. Advances in Parasitology 75, 193–208.CrossRefGoogle ScholarPubMed
Jones, K, Versteeg, L, Damania, A, Keegan, B, Kendricks, A, Pollet, J, Cruz-Chan, JV, Gusovsky, F, Hotez, PJ and Bottazzi, ME (2018) Vaccine-linked chemotherapy improves benznidazole efficacy for acute Chagas disease. Infection and Immunity 86, e00876–e00817.CrossRefGoogle ScholarPubMed
Lemańska-Perek, A and Adamik, B (2019) Fibronectin and its soluble EDA-FN isoform as biomarkers for inflammation and sepsis. Advances in Clinical and Experimental Medicine 28, 1561–1567.CrossRefGoogle ScholarPubMed
Maeda, FY, Cortez, C, Izidoro, MA, Juliano, L and Yoshida, N (2014) Fibronectin-degrading activity of Trypanosoma cruzi cysteine proteinase plays a role in host cell invasion. Infection and Immunity 82, 5166–5174.CrossRefGoogle Scholar
Maurer, LM, Ma, W and Mosher, DF (2015) Dynamic structure of plasma fibronectin. Critical Reviews in Biochemistry and Molecular Biology 51, 213–227.CrossRefGoogle ScholarPubMed
Molina, I, Salvador, F, Sánchez-Montalvá, A, Treviño, B, Serre, N, Sao Avilés, A and Almirante, B (2015) Toxic profile of benznidazole in patients with chronic Chagas disease: risk factors and comparison of the product from two different manufacturers. Antimicrobial Agents and Chemotherapy 59, 6125–6131.CrossRefGoogle ScholarPubMed
Mosesson, MW and Umfleet, RA (1970) The cold-insoluble globulin of human plasma. I. Purification, primary characterization, and relationship to fibrinogen and other cold-insoluble fraction components. Journal of Biological Chemistry 245, 5728–5736.CrossRefGoogle ScholarPubMed
Ndao, M, Spithill, TW, Caffrey, R, Li, H, Podust, VN, Perichon, R, Santamaria, C, Ache, A, Duncan, M, Powell, MR and Ward, BJ (2010) Identification of novel diagnostic serum biomarkers for Chagas’ disease in asymptomatic subjects by mass spectrometric profiling. Journal of Clinical Microbiology 48, 1139–1149.CrossRefGoogle ScholarPubMed
Osorio, L, Ríos, I, Gutiérrez, B and González, J (2012) Virulence factors of Trypanosoma cruzi: who is who? Microbes and Infection 14, 1390–1402.CrossRefGoogle ScholarPubMed
Pankov, R and Yamada, KM (2002) Fibronectin at a glance. Journal of Cell Science 115, 3861–3863.CrossRefGoogle ScholarPubMed
Pinazo, M-J, Thomas, MC, Bua, J, Perrone, A, Schijman, A-G, Viotti, R-J, Ramsey, J-M, Ribeiro, I, Sosa-Estani, S, López, M-C and Gascon, J (2014) Biological markers for evaluating therapeutic efficacy in Chagas disease, a systematic review. Expert Review of Anti-infective Therapy 12, 479–496.CrossRefGoogle ScholarPubMed
Pinazo, M-J, Thomas, M-C, Bustamante, J, de Almeida, IC, Lopez, M-C and Gascon, J (2015) Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives. Memórias do Instituto Oswaldo Cruz 110, 422–432.CrossRefGoogle ScholarPubMed
Pinazo, M-J, Posada, EDJ, Izquierdo, L, Tassies, D, Marques, A-F, de Lazzari, E, Aldasoro, E, Muñoz, J, Abras, A, Tebar, S, Gallego, M, de Almeida, IC, Reverter, J-C and Gascon, J (2016) Altered hypercoagulability factors in patients with chronic Chagas disease: potential biomarkers of therapeutic response. PLoS Neglected Tropical Diseases 10, e0004269.CrossRefGoogle ScholarPubMed
Pinho, RT, Waghabi, MC, Cardillo, F, Mengel, J and Antas, PRZ (2016) Scrutinizing the biomarkers for the neglected Chagas disease: how remarkable!. Frontiers in Immunology 7, 306.CrossRefGoogle ScholarPubMed
Porrás, AI, Yadon, ZE, Altcheh, J, Britto, C, Chaves, GC, Flevaud, L, Martins-Filho, OA, Ribeiro, I, Schijman, AG, Shikanai-Yasuda, MA, Sosa-Estani, S, Stobbaerts, E and Zicker, F (2015) Target product profile (TPP) for Chagas disease point-of-care diagnosis and assessment of response to treatment. PLoS Neglected Tropical Diseases 9, e0003697.CrossRefGoogle ScholarPubMed
Quijano-Hernández, IA, Castro-Barcena, A, Vázquez-Chagoyán, JC, Bolio-González, ME, Ortega-López, J and Dumonteil, E (2013) Preventive and therapeutic DNA vaccination partially protect dogs against an infectious challenge with Trypanosoma cruzi. Vaccine 31, 2246–2252.CrossRefGoogle ScholarPubMed
Ruiz-Lancheros, E, Rasoolizadeh, A, Chatelain, E, Garcia-Bournissen, F, Moroni, S, Moscatelli, G, Altcheh, J and Ndao, M (2018) Validation of apolipoprotein A-1 and fibronectin fragments as markers of parasitological cure for congenital Chagas disease in children treated with Benznidazole. Open Forum Infectious Diseases 5, ofy236–ofy236.CrossRefGoogle ScholarPubMed
Santamaria, C, Chatelain, E, Jackson, Y, Miao, Q, Ward, BJ, Chappuis, F and Ndao, M (2014) Serum biomarkers predictive of cure in Chagas disease patients after nifurtimox treatment. BMC Infectious Diseases 14, 302–302.CrossRefGoogle ScholarPubMed
Sguassero, Y, Roberts, KN, Harvey, GB, Comandé, D, Ciapponi, A, Cuesta, CB, Aguiar, C, Castro, AM, Danesi, E, de Andrade, AL, de Lana, M, Escribà, JM, Fabbro, DL, Fernandes, CD, Flores-Chávez, M, Hasslocher-Moreno, AM, Jackson, Y, Lacunza, CD, Machado-de-Assis, GF, Maldonado, M, Meira, WSF, Molina, I, Monje-Rumi, MM, Muñoz-San Martín, C, Murcia, L, Nery de Castro, C, Sánchez Negrette, O, Segovia, M, Silveira, CAN, Solari, A, Steindel, M, Streiger, ML, Vera de Bilbao, N, Zulantay, I and and Sosa-Estani, S (2018) Course of serological tests in treated subjects with chronic Trypanosoma cruzi infection: a systematic review and meta-analysis of individual participant data. International Journal of Infectious Diseases 73, 93–101.CrossRefGoogle ScholarPubMed
Sherbuk, JE, Okamoto, EE, Marks, MA, Fortuny, E, Clark, EH, Galdos-Cardenas, G, Vasquez-Villar, A, Fernandez, AB, Crawford, TC, Do, RQ, Flores-Franco, JL, Colanzi, R, Gilman, RH and Bern, C (2015) Biomarkers and mortality in severe Chagas cardiomyopathy. Global Heart 10, 173–180.CrossRefGoogle ScholarPubMed
Song, J, Tan, H, Perry, AJ, Akutsu, T, Webb, GI, Whisstock, JC and Pike, RN (2012) PROSPER: an integrated feature-based tool for predicting protease substrate cleavage sites. PLoS ONE 7, e50300.CrossRefGoogle ScholarPubMed
Song, J, Li, F, Leier, A, Marquez-Lago, TT, Akutsu, T, Haffari, G, Chou, K-C, Webb, GI and Pike, RN (2017) Prosperous: high-throughput prediction of substrate cleavage sites for 90 proteases with improved accuracy. Bioinformatics 34, 684–687.CrossRefGoogle Scholar
Speziale, P, Arciola, CR and Pietrocola, G (2019) Fibronectin and its role in human infective diseases. Cells 8, 1516. https://doi.org/10.3390/cells8121516CrossRefGoogle ScholarPubMed
Sulleiro, E, Muñoz-Calderon, A and Schijman, AG (2019) Role of nucleic acid amplification assays in monitoring treatment response in Chagas disease: usefulness in clinical trials. Acta Tropica 199, 105120.CrossRefGoogle ScholarPubMed
Urbina, JA (2015) Recent clinical trials for the etiological treatment of chronic Chagas disease: advances, challenges and perspectives. Journal of Eukaryotic Microbiology 62, 149–156.CrossRefGoogle Scholar
Wang, Y and Ni, H (2016) Fibronectin maintains the balance between hemostasis and thrombosis. Cellular and Molecular Life Sciences 73, 3265–3277.CrossRefGoogle ScholarPubMed
Zardi, L, Cecconi, C, Barbieri, O, Carnemolla, B, Picca, M and Santi, L (1979) Concentration of fibronectin in plasma of tumor-bearing mice and synthesis by Ehrlich ascites tumor cells. Cancer Research 39, 3774–3779.Google ScholarPubMed