Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype

Eradication of bovine tuberculosis (bTB) continues to be a worldwide challenge. The lack of reliable vaccines dampens the control and eradication programs of Mycobacterium bovis infection and spread. Selection and breeding of cattle resistant to M. bovis infection would greatly enhance the effective...

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Autores principales:	Jorge Luis Mazorra-Carrillo, Omar Antonio Alcaraz-López, Gonzalo López-Rincón, Bernardo Villarreal-Ramos, José A. Gutiérrez-Pabello, Hugo Esquivel-Solís
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	host resistance to infection Mycobacterium bovis bovine tuberculosis biomarkers proteome ELISA Veterinary medicine SF600-1100
Acceso en línea:	https://doaj.org/article/ed160667ac1c49809d0ace07cc06a3b9
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spelling	oai:doaj.org-article:ed160667ac1c49809d0ace07cc06a3b92021-11-18T09:07:15ZHost Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype2297-176910.3389/fvets.2021.734087https://doaj.org/article/ed160667ac1c49809d0ace07cc06a3b92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fvets.2021.734087/fullhttps://doaj.org/toc/2297-1769Eradication of bovine tuberculosis (bTB) continues to be a worldwide challenge. The lack of reliable vaccines dampens the control and eradication programs of Mycobacterium bovis infection and spread. Selection and breeding of cattle resistant to M. bovis infection would greatly enhance the effectiveness of bTB eradication programs. Here, we have evaluated the potential of serum proteins as biomarkers of cattle resistance to bTB in Holstein-Friesian cows, 6–8-year-old, born and raised in similar conditions in herds with bTB prevalence >30%. Serum proteins obtained from uninfected cows (bTB-resistant; R) were compared to those from infected cows (bTB-susceptible; S), defined by a negative or positive bTB diagnosis, respectively. bTB diagnosis included: (i) single intradermal (caudal fold) tuberculin test, (ii) whole blood IFN-gamma test, (iii) gross visible lesions in lymph nodes and lungs by inspection at the abattoir, and (iv) a bacteriological culture for M. bovis. Using 2D-GE and LC-ESI-MS/MS, we found higher expression levels of primary amine oxidase (AO), complement component 5 (C5), and serotransferrin (TF) in R cattle than S cattle. In-house developed and standardized ELISAs for these novel biomarkers showed the best sensitivities of 72, 77, 77%, and specificities of 94, 94, 83%, for AO, C5, and TF, respectively. AUC-ROC (95% CI) values of 0.8935 (0.7906–0.9964), 0.9290 (0.8484–1.010), and 0.8580 (0.7291–0.9869) were obtained at cut-off points of 192.0, 176.5 ng/ml, and 2.1 mg/ml for AO, C5, and TF, respectively. These proteins are involved in inflammatory/immunomodulatory responses to infections and may provide a novel avenue of research to determine the mechanisms of protection against bTB. Overall, our results indicate that these proteins could be novel biomarkers to help identify cattle resistant to bTB, which in turn could be used to strengthen the effectiveness of existing eradication programs against bTB.Jorge Luis Mazorra-CarrilloOmar Antonio Alcaraz-LópezOmar Antonio Alcaraz-LópezGonzalo López-RincónBernardo Villarreal-RamosBernardo Villarreal-RamosJosé A. Gutiérrez-PabelloHugo Esquivel-SolísFrontiers Media S.A.articlehost resistance to infectionMycobacterium bovisbovine tuberculosisbiomarkersproteomeELISAVeterinary medicineSF600-1100ENFrontiers in Veterinary Science, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	host resistance to infection Mycobacterium bovis bovine tuberculosis biomarkers proteome ELISA Veterinary medicine SF600-1100
spellingShingle	host resistance to infection Mycobacterium bovis bovine tuberculosis biomarkers proteome ELISA Veterinary medicine SF600-1100 Jorge Luis Mazorra-Carrillo Omar Antonio Alcaraz-López Omar Antonio Alcaraz-López Gonzalo López-Rincón Bernardo Villarreal-Ramos Bernardo Villarreal-Ramos José A. Gutiérrez-Pabello Hugo Esquivel-Solís Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype
description	Eradication of bovine tuberculosis (bTB) continues to be a worldwide challenge. The lack of reliable vaccines dampens the control and eradication programs of Mycobacterium bovis infection and spread. Selection and breeding of cattle resistant to M. bovis infection would greatly enhance the effectiveness of bTB eradication programs. Here, we have evaluated the potential of serum proteins as biomarkers of cattle resistance to bTB in Holstein-Friesian cows, 6–8-year-old, born and raised in similar conditions in herds with bTB prevalence >30%. Serum proteins obtained from uninfected cows (bTB-resistant; R) were compared to those from infected cows (bTB-susceptible; S), defined by a negative or positive bTB diagnosis, respectively. bTB diagnosis included: (i) single intradermal (caudal fold) tuberculin test, (ii) whole blood IFN-gamma test, (iii) gross visible lesions in lymph nodes and lungs by inspection at the abattoir, and (iv) a bacteriological culture for M. bovis. Using 2D-GE and LC-ESI-MS/MS, we found higher expression levels of primary amine oxidase (AO), complement component 5 (C5), and serotransferrin (TF) in R cattle than S cattle. In-house developed and standardized ELISAs for these novel biomarkers showed the best sensitivities of 72, 77, 77%, and specificities of 94, 94, 83%, for AO, C5, and TF, respectively. AUC-ROC (95% CI) values of 0.8935 (0.7906–0.9964), 0.9290 (0.8484–1.010), and 0.8580 (0.7291–0.9869) were obtained at cut-off points of 192.0, 176.5 ng/ml, and 2.1 mg/ml for AO, C5, and TF, respectively. These proteins are involved in inflammatory/immunomodulatory responses to infections and may provide a novel avenue of research to determine the mechanisms of protection against bTB. Overall, our results indicate that these proteins could be novel biomarkers to help identify cattle resistant to bTB, which in turn could be used to strengthen the effectiveness of existing eradication programs against bTB.
format	article
author	Jorge Luis Mazorra-Carrillo Omar Antonio Alcaraz-López Omar Antonio Alcaraz-López Gonzalo López-Rincón Bernardo Villarreal-Ramos Bernardo Villarreal-Ramos José A. Gutiérrez-Pabello Hugo Esquivel-Solís
author_facet	Jorge Luis Mazorra-Carrillo Omar Antonio Alcaraz-López Omar Antonio Alcaraz-López Gonzalo López-Rincón Bernardo Villarreal-Ramos Bernardo Villarreal-Ramos José A. Gutiérrez-Pabello Hugo Esquivel-Solís
author_sort	Jorge Luis Mazorra-Carrillo
title	Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype
title_short	Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype
title_full	Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype
title_fullStr	Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype
title_full_unstemmed	Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype
title_sort	host serum proteins as potential biomarkers of bovine tuberculosis resistance phenotype
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ed160667ac1c49809d0ace07cc06a3b9
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Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype

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