Evaluation of polymorphisms at the 3´ UTR SLC11A1 gene microsatellites and their associations with the outcome of Brucella abortus infection in Bos taurus cattle

In ruminants, polymorphisms in microsatellites at 3´untranslated region (3´ UTR) of the SLC11A1 gene were associated with natural resistance to Brucella spp. and Mycobacterium spp. infection, but its relevance to prevent brucellosis is controversial in cattle. The aim of this study was to re-evaluat...

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Main Authors: Hasenauer, Flavia Carolina, Caffaro, María Eugenia, Poli, Mario Andres, Rossetti, Carlos Alberto
Format: Artículo
Language:Inglés
Published: Ediciones INTA 2022
Subjects:
Online Access:http://hdl.handle.net/20.500.12123/13486
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author Hasenauer, Flavia Carolina
Caffaro, María Eugenia
Poli, Mario Andres
Rossetti, Carlos Alberto
author_browse Caffaro, María Eugenia
Hasenauer, Flavia Carolina
Poli, Mario Andres
Rossetti, Carlos Alberto
author_facet Hasenauer, Flavia Carolina
Caffaro, María Eugenia
Poli, Mario Andres
Rossetti, Carlos Alberto
author_sort Hasenauer, Flavia Carolina
collection INTA Digital
description In ruminants, polymorphisms in microsatellites at 3´untranslated region (3´ UTR) of the SLC11A1 gene were associated with natural resistance to Brucella spp. and Mycobacterium spp. infection, but its relevance to prevent brucellosis is controversial in cattle. The aim of this study was to re-evaluate the role of these polymorphisms in the outcome of Brucella abortus infection in European bovine breeds. Initially, the presence or absence of specific antibodies against Brucella abortus in beef (n=74) or dairy (n=69) Bos taurus cattle at high risk of natural Brucella infection was used to identify susceptible (cases, infected) or resistant (control, non-infected) animals. Then, innate resistance to Brucella infection was evaluated in B. taurus peripheral blood monocyte-derived macrophages (MDMs) challenged with the pathogen. Finally, a bioinformatics analysis of the 3′ UTR of the SLC11A1 gene was performed to evaluate its putative functional impact on gene regulation. Fifty four (54) brucellosis positive and 89 brucellosis negative animals were genotyped for both microsatellites by multiplex PCR-capillary electrophoresis. Our results showed that the homozygous genotypes 159 and 175 for Ms1 and Ms2 respectively, previously defined as “resistant” genotypes, were the most frequent among the animal population. Independently, no association was detected between these or other polymorphisms and the absence or presence of humoral immune response against brucellosis. Moreover, no association was observed between the resistant genotype with the restricted B. abortus-intracellular growth phenotype in MDMs. In silico analysis of 3′ UTR sequence predicted two canonical binding sites for transcriptional regulatory elements belonging to TEF-1 and SMAD families, but most importantly, the secondary structure of the 3’UTR remains unchanged regardless of the length of the microsatellites. Taken together, these results show no evidence of an association between the 3’UTR SLC11A1 polymorphisms and natural resistance against brucellosis in cattle.
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spelling INTA134862022-11-30T11:43:08Z Evaluation of polymorphisms at the 3´ UTR SLC11A1 gene microsatellites and their associations with the outcome of Brucella abortus infection in Bos taurus cattle Hasenauer, Flavia Carolina Caffaro, María Eugenia Poli, Mario Andres Rossetti, Carlos Alberto Ganado Bovino Bos taurus Polimorfismo Microsatélites Brucella abortus Enfermedades de los Animales Brucelosis Cattle Polymorphism Microsatellites Animal Diseases Brucellosis In ruminants, polymorphisms in microsatellites at 3´untranslated region (3´ UTR) of the SLC11A1 gene were associated with natural resistance to Brucella spp. and Mycobacterium spp. infection, but its relevance to prevent brucellosis is controversial in cattle. The aim of this study was to re-evaluate the role of these polymorphisms in the outcome of Brucella abortus infection in European bovine breeds. Initially, the presence or absence of specific antibodies against Brucella abortus in beef (n=74) or dairy (n=69) Bos taurus cattle at high risk of natural Brucella infection was used to identify susceptible (cases, infected) or resistant (control, non-infected) animals. Then, innate resistance to Brucella infection was evaluated in B. taurus peripheral blood monocyte-derived macrophages (MDMs) challenged with the pathogen. Finally, a bioinformatics analysis of the 3′ UTR of the SLC11A1 gene was performed to evaluate its putative functional impact on gene regulation. Fifty four (54) brucellosis positive and 89 brucellosis negative animals were genotyped for both microsatellites by multiplex PCR-capillary electrophoresis. Our results showed that the homozygous genotypes 159 and 175 for Ms1 and Ms2 respectively, previously defined as “resistant” genotypes, were the most frequent among the animal population. Independently, no association was detected between these or other polymorphisms and the absence or presence of humoral immune response against brucellosis. Moreover, no association was observed between the resistant genotype with the restricted B. abortus-intracellular growth phenotype in MDMs. In silico analysis of 3′ UTR sequence predicted two canonical binding sites for transcriptional regulatory elements belonging to TEF-1 and SMAD families, but most importantly, the secondary structure of the 3’UTR remains unchanged regardless of the length of the microsatellites. Taken together, these results show no evidence of an association between the 3’UTR SLC11A1 polymorphisms and natural resistance against brucellosis in cattle. Los polimorfismos presentes en los microsatélites de la región 3’UTR del gen SLC11A1 de los rumiantes fue asociada a la resistencia natural a la infección por Brucella spp. y Mycobacterium spp., aunque su relevancia en la prevención de la brucelosis bovina es controversial. El objetivo de este estudio fue reevaluar el rol de esos polimorfismos frente a una infección por B. abortus en bovinos de razas europeas. Inicialmente se utilizó la presencia o ausencia de anticuerpos específicos anti B. abortus en bovinos de carne (n=74) o leche (n=69) con alto riesgo de infección natural para identificar animales susceptibles (casos, infectados) o resistentes (controles, no infectados) a la infección. Posteriormente, la resistencia innata a la infección por B. abortus fue evaluada en macrófagos derivados de monocitos sanguíneos (MDMs) desafiados con la bacteria. Finalmente, se realizó un análisis bioinformático de la porción 3’UTR del gen SLC11A1 para evaluar el impacto funcional en la regulación del gen. Se genotiparon por electroforesis capilar– PCR multiplex para ambos microsatélites, 54 animales serológicamente positivos y 89 negativos a brucelosis. Nuestros resultados mostraron que los genotipos 159 y 175 para los Ms1 y Ms2 respectivamente, previamente definidos como “resistentes”, fueron los más frecuentes entre la población estudiada. Independientemente de esto, no se detectó asociación entre estos u otros polimorfismos con la ausencia o presencia de respuesta inmune humoral a Brucella. Tampoco se observó asociación entre los genotipos resistentes y el fenotipo de crecimiento de B. abortus en MDMs. El análisis in silico de la secuencia 3’ UTR predijo dos sitios de unión canónicos para elementos reguladores transcripcionales pertenecientes a las familias TEF-1 y SMAD, además de indicar que la estructura secundaria de esa porción génica permanecía inalterable independientemente de la extensión de los microsatélites. En conjunto, estos resultados indican una falta de asociación entre los polimorfismos en la porción 3’UTR del gen SLC11A1 y la resistencia natural a la brucelosis en los bovinos de origen europeos. Instituto de Patobiología Fil: Hasenauer, Flavia Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina Fil: Hasenauer, Flavia Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Hasenauer, Flavia Carolina. Université Paris Cité, CNRS, INSERM; Francia Fil: Caffaro, Marí­a Eugenia. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina Fil: Poli, Mario Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética; Argentina Fil: Rossetti, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina 2022-11-30T11:38:54Z 2022-11-30T11:38:54Z 2022-11 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/13486 1669-2314 0325-8718 eng info:eu-repograntAgreement/INTA/PNBIO-1131033/AR./Genómica y biotecnología aplicada a la cría animal. info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Ediciones INTA RIA 48 (3) : 215-223 (noviembre 2022)
spellingShingle Ganado Bovino
Bos taurus
Polimorfismo
Microsatélites
Brucella abortus
Enfermedades de los Animales
Brucelosis
Cattle
Polymorphism
Microsatellites
Animal Diseases
Brucellosis
Hasenauer, Flavia Carolina
Caffaro, María Eugenia
Poli, Mario Andres
Rossetti, Carlos Alberto
Evaluation of polymorphisms at the 3´ UTR SLC11A1 gene microsatellites and their associations with the outcome of Brucella abortus infection in Bos taurus cattle
title Evaluation of polymorphisms at the 3´ UTR SLC11A1 gene microsatellites and their associations with the outcome of Brucella abortus infection in Bos taurus cattle
title_full Evaluation of polymorphisms at the 3´ UTR SLC11A1 gene microsatellites and their associations with the outcome of Brucella abortus infection in Bos taurus cattle
title_fullStr Evaluation of polymorphisms at the 3´ UTR SLC11A1 gene microsatellites and their associations with the outcome of Brucella abortus infection in Bos taurus cattle
title_full_unstemmed Evaluation of polymorphisms at the 3´ UTR SLC11A1 gene microsatellites and their associations with the outcome of Brucella abortus infection in Bos taurus cattle
title_short Evaluation of polymorphisms at the 3´ UTR SLC11A1 gene microsatellites and their associations with the outcome of Brucella abortus infection in Bos taurus cattle
title_sort evaluation of polymorphisms at the 3´ utr slc11a1 gene microsatellites and their associations with the outcome of brucella abortus infection in bos taurus cattle
topic Ganado Bovino
Bos taurus
Polimorfismo
Microsatélites
Brucella abortus
Enfermedades de los Animales
Brucelosis
Cattle
Polymorphism
Microsatellites
Animal Diseases
Brucellosis
url http://hdl.handle.net/20.500.12123/13486
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