Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-10T10:11:53.011Z Has data issue: false hasContentIssue false

Going further post-RNA-seq: In silico functional analyses revealing candidate genes and regulatory elements related to mastitis in dairy cattle

Published online by Cambridge University Press:  10 August 2021

Hyago Passe Pereira
Affiliation:
Institute of Biological Sciences, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil
Lucas Lima Verardo
Affiliation:
Zootechnics Department, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Brazil
Mayara Morena Del Cambre Amaral Weller
Affiliation:
Zootechnics Department, Universidade Federal do Espírito Santo, Alegre, Brazil
Ana Paula Sbardella
Affiliation:
Department of Exact Sciences, Universidade Estadual Paulista Júlio de Mesquita Filho, Jaboticabal, Brazil
Danísio Prado Munari
Affiliation:
Department of Exact Sciences, Universidade Estadual Paulista Júlio de Mesquita Filho, Jaboticabal, Brazil
Raquel Morais de Paiva Daibert
Affiliation:
Molecular Genetics Laboratory, Embrapa Gado de Leite, Juiz de Fora, Brazil
Wanessa Araújo Carvalho
Affiliation:
Molecular Genetics Laboratory, Embrapa Gado de Leite, Juiz de Fora, Brazil
Marco Antonio Machado
Affiliation:
Molecular Genetics Laboratory, Embrapa Gado de Leite, Juiz de Fora, Brazil
Marta Fonseca Martins*
Affiliation:
Molecular Genetics Laboratory, Embrapa Gado de Leite, Juiz de Fora, Brazil
*
Author for correspondence: Marta Fonseca Martins, Email: marta.martins@embrapa.br

Abstract

This study aimed to obtain a better understanding of the regulatory genes and molecules involved in the development of mastitis. For this purpose, the transcription factors (TF) and MicroRNAs (miRNA) related to differentially expressed genes previously found in extracorporeal udders infected with Streptococcus agalactiae were investigated. The Gene-TF network highlighted LOC515333, SAA3, CD14, NFKBIA, APOC2 and LOC100335608 and genes that encode the most representative transcription factors STAT3, PPARG, EGR1 and NFKB1 for infected udders. In addition, it was possible to highlight, through the analysis of the gene-miRNA network, genes that could be post-transcriptionally regulated by miRNAs, such as the relationship between the CCL5 gene and the miRNA bta-miR-363. Overall, our data demonstrated genes and regulatory elements (TF and miRNA) that can play an important role in mastitis resistance. The results provide new insights into the first functional pathways and the network of genes that orchestrate the innate immune responses to infection by Streptococcus agalactiae. Our results will increase the general knowledge about the gene networks, transcription factors and miRNAs involved in fighting intramammary infection and maintaining tissue during infection and thus enable a better understanding of the pathophysiology of mastitis.

Type
Research Article
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press on behalf of Hannah Dairy Research Foundation

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Anders, S, Pyl, PT and Huber, W (2014) HTSeq – A Python framework to work with high-throughput sequencing data. Bioinformatics 31, 14.Google ScholarPubMed
Bindea, G, Mlecnik, B, Hackl, H, Charoentong, P, Tosolini, M, Kirilovsky, A, Fridman, WH, Pagès, F, Trajanoski, Z and Galon, J (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics (Oxford, England) 25, 10911093.CrossRefGoogle ScholarPubMed
Bannerman, DD (2009) Pathogen-dependent induction of cytokines and other soluble inflammatory mediators during intramammary infection of dairy cows. Journal of Animal Science 87, 1025.CrossRefGoogle ScholarPubMed
Bannerman, DD, Paape, MJ, Lee, JW, Zhao, X, Hope, JC and Rainard, P (2004a) Escherichia coli and Staphylococcus aureus elicit differential innate immune responses following intramammary infection. Clinical and Diagnostic Laboratory Immunology 11, 463472.Google Scholar
Bannerman, DD, Paape, MJ, Goff, JP, Kimura, K, Lippolis, JD, Hope, JC (2004b) Innate immune response to intramammary infection with Serratia marcescens and Streptococcus uberis. Veterinary Research 35, 681700.CrossRefGoogle Scholar
Contreras, GA and Rodríguez, JM (2011) Mastitis: comparative etiology and epidemiology. Journal of Mammary Gland Biology and Neoplasia 16, 339356.CrossRefGoogle ScholarPubMed
Duarte, RS, Miranda, OP, Bellei, BC, Brito, MAV and Teixeira, LM (2004) Phenotypic and molecular characteristics of Streptococcus agalactiae isolates recovered from milk of dairy cows in Brazil. Journal of Clinical Microbiology 42, 42144222.CrossRefGoogle ScholarPubMed
Eckersall, PD, Young, FJ, McComb, C, Hogarth, CJ, Safi, S, Fitzpatrick, JL, Nolan, AM, Weber, A and McDonald, T (2001) Acute phase proteins in serum and milk from dairy cows with clinical mastitis. Veterinary Record 148, 3541.CrossRefGoogle ScholarPubMed
Eckersall, PD, Young, FJ, Nolan, AM, Knight, CH, McComb, C, Waterston, MM, Hogarth, CJ, Scott, EM and Fitzpatrick, JL (2006) Acute phase proteins in bovine milk in an experimental model of Staphylococcus aureus subclinical mastitis. Journal of Dairy Science 89, 14881501.CrossRefGoogle Scholar
Fonseca, I, Cardoso, FF, Higa, RH, Giachetto, PF, Brandão, HDM, Brito, MAVP, Ferreira, MBD, Guimarães, SEF and Martins, MF (2015) Gene expression profile in zebu dairy cows (Bos taurus indicus) with mastitis caused by Streptococcus agalactiae. Livestock Science 180, 4757.CrossRefGoogle Scholar
Gao, D, Rahbar, R and Fish, EM (2016) CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells. Open Biology 6, 160122.CrossRefGoogle ScholarPubMed
Günther, J, Koy, M, Berthold, A, Schuberth, HJ and Seyfert, HM (2016) Comparison of the pathogen species-specific immune response in udder derived cell types and their models. Veterinary Research 47, 22.CrossRefGoogle ScholarPubMed
Guterbock, WM, Van Eenennaam, AL, Anderson, RJ, Gardner, IA, Cullor, JS and Holmberg, CA (1993) Efficacy of intramammary antibiotic therapy for treatment of clinical mastitis caused by environmental pathogens. Journal of Dairy Science 76, 34373444.CrossRefGoogle ScholarPubMed
Keefe, GP (1997) Streptococcus agalactiae mastitis: a review. The Canadian Veterinary Journal 38, 429.Google ScholarPubMed
Kosciuczuk, EM, Lisowski, P, Jarczak, J, Majewska, A, Rzewuska, M, Zwierzchowski, L and Bagnicka, E (2017) Transcriptome profiling of Staphylococci-infected cow mammary gland parenchyma. BMC Veterinary Research 13, 161.CrossRefGoogle ScholarPubMed
Lee, GR (2018) The balance of Th17 vs. Treg cells in autoimmunity. International Journal of Molecular Sciences 19, 730.CrossRefGoogle Scholar
Li, C, Sun, D, Zhang, S, Wang, S, Wu, X, Zhang, Q, Liu, L, Li, Y and Qiao, L (2014) Genome wide association study identifies 20 novel promising genes associated with milk fatty acid traits in Chinese Holstein. PloS One 9, e96186.CrossRefGoogle ScholarPubMed
Lutzow, YCS, Donaldson, L, Gray, CP, Vuocolo, T, Pearson, RD, Reverter, A, Byrne, KA, Sheehy, PA, Windon, R and Tellam, RL (2008) Identification of immune genes and proteins involved in the response of bovine mammary tissue to Staphylococcus aureus infection. BMC Veterinary Research 4, 18.CrossRefGoogle ScholarPubMed
Maere, S, Heymans, K and Kuiper, M (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics (Oxford, England) 21, 34483449.CrossRefGoogle ScholarPubMed
Matsunaga, K, Taoka, M, Isobe, T and Izumi, T (2017) Rab2a and Rab27a cooperatively regulate the transition from granule maturation to exocytosis through the dual effector Noc2. Journal of Cell Science 130, 541550.Google ScholarPubMed
Molenaar, AJ, Harris, DP, Rajan, GH, Pearson, ML, Callaghan, MR, Sommer, L, Farr, VC, Oden, KE, Miles, MC, Petrova, RS, Good, LL, Singh, K, McLaren, RD, Prosser, CG, Kim, KS, Wieliczko, RJ, Dines, MH, Johannessen, KM, Grigor, MR, Davis, SR and Stelwagen, K (2009) The acute-phase protein serum amyloid A3 is expressed in the bovine mammary gland and plays a role in host defense. Biomarkers 14, 2637.CrossRefGoogle Scholar
Moyes, KM, Drackley, JK, Morin, DE, Bionaz, M, Rodriguez-Zas, SL, Everts, RE, Lewin, HA and Loor, JJ (2009) Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPARγ signaling as potential mechanism for the negative relationships between immune response and lipid metabolism. BMC Genomics 10, 542.CrossRefGoogle ScholarPubMed
Oviedo-Boyso, J, Valdez-Alarcón, JJ, Cajero-Juárez, M, Ochoa-Zarzosa, A, López-Meza, JE, Bravo-Patino, A and Baizabal-Aguirre, VM (2007) Innate immune response of bovine mammary gland to pathogenic bacteria responsible for mastitis. Journal of Infection 54, 399409.CrossRefGoogle ScholarPubMed
Petzl, W, Zerbe, H, Günther, J, Yang, W, Seyfert, HM, Nürnberg, G and Schuberth, HJ (2008) Escherichia coli, but not Staphylococcus aureus triggers an early increased expression of factors contributing to the innate immune defense in the udder of the cow. Veterinary Researc 39, 123.Google Scholar
Pinto, ISB, Fonseca, I, Brandao, HDM, Gern, JC, Guimarães, AS, Carvalho, WA, Brito, MAVP, Viccini, LF and Martins, MF (2017) Short communication: evaluation of perfused bovine udder for gene expression studies in dairy cows. Genetic and Molecular Research 16, gmr16019637.CrossRefGoogle ScholarPubMed
Portnoy, V, Huang, V, Place, RF and Li, LC (2011) Small RNA and transcriptional upregulation. Wiley Interdisciplinary Reviews: RNA 2, 748760.CrossRefGoogle ScholarPubMed
Putcha, BDK, Jia, X, Katkoori, VR, Salih, C, Shanmugam, C, Jadhav, T, Bovell, LC, Behring, MP, Callens, T, Messiaen, L, Bae, S, Grizzle, WE, Singh, KP and Manne, U (2015) Clinical implications of rabphillin-3A-like gene alterations in breast cancer. PloS One 10, e0129216.CrossRefGoogle ScholarPubMed
Robinson, MD, McCarthy, DJ and Smyth, GK (2010) edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics (Oxford, England) 26, 139140.CrossRefGoogle ScholarPubMed
Rosales, C, Lowell, CA, Schnoor, M and Uribe-Querol, E (2017) Neutrophils: their role in innate and adaptive immunity 2017. Journal of Immunology Research 2017, 9748345.CrossRefGoogle ScholarPubMed
Sandelin, A, Alkema, W, Engström, P, Wasserman, WW and Lenhard, B (2004) JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Research 32, 9194.CrossRefGoogle ScholarPubMed
Sbardella, AP, Weller, MMDCA, Fonseca, I, Stafuzza, NB, Bernardes, PA, Silva, FF, da Silva, MVGB, Martins, MF and Munari, DP (2019) RNA sequencing differential gene expression analysis of isolated perfused bovine udders experimentally inoculated with Streptococcus agalactiae. Journal of Dairy Science 102, 7611767.CrossRefGoogle ScholarPubMed
Shannon, P, Markiel, A, Ozier, O, Baliga, NS, Wang, JT, Ramage, D, Amin, N, Schwikowsk, B and Ideker, T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research 13, 24982504.CrossRefGoogle ScholarPubMed
Shin, MK, Park, HT, Shin, SW, Jung, M, Im, YB, Park, HE, Cho, YI and Yoo, HS (2015) Whole-blood gene-expression profiles of cows infected with Mycobacterium avium subsp. paratuberculosis reveal changes in immune response and lipid metabolism. Journal of Microbiology and Biotechnology 2, 255267.CrossRefGoogle Scholar
Swanson, KM, Stelwagen, K, Dobson, J, Henderson, HV, Davis, SR, Farr, VC and Singh, K (2009) Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model. Journal of Dairy Science 92, 117129.CrossRefGoogle Scholar
Tegowski, M, Fan, C and Baldwin, AS (2018) Thioridazine inhibits self-renewal in breast cancer cells via DRD2-dependent STAT3 inhibition, but induces a G1 arrest independent of DRD2. Journal of Biological Chemistry 41, 1597715990.CrossRefGoogle Scholar
Thorgersen, EB, Hellerud, BC, Nielsen, EW, Barratt-Due, A, Fure, H, Lindstad, JK, Pharo, A, Fosse, E, Tønnessen, TI, Johansen, HT, Castellheim, A and Mollnes, TE (2010) CD14 inhibition efficiently attenuates early inflammatory and hemostatic responses in Escherichia coli sepsis in pigs. The FASEB Journal 24, 712722.CrossRefGoogle ScholarPubMed
Touzet, H and Varré, JS (2007) Efficient and accurate P-value computation for Position Weight Matrices. Algorithms for Molecular Biology 2, 15.CrossRefGoogle ScholarPubMed
Wang, YL, Guo, XY, He, W, Chen, RJ and Zhuang, R (2017) Effects of alliin on LPS-induced acute lung injury by activating PPARγ. Microbial Pathogenesis 110, 375379.CrossRefGoogle ScholarPubMed
Weller, MMDCA, Fonseca, I, Sbardella, AP, Pinto, IS, Viccini, LF, Brandão, HM, Gern, JC, Carvalho, WA, Guimarães, AS, Brito, MAVP, Munari, DP, Silva, MVGB and Martins, MF (2019) Isolated perfused udder model for transcriptome analysis in response to Streptococcus agalactiae. Journal of Dairy Research 86, 307314.CrossRefGoogle ScholarPubMed
Wilson, DJ, Gonzalez, RN, Case, KL, Garrison, LL and Groöhn, YT (1999) Comparison of seven antibiotic treatments with no treatment for bacteriological efficacy against bovine mastitis pathogens. Journal of Dairy Science 82, 16641670.CrossRefGoogle ScholarPubMed
Zadoks, RN, Middleton, JR, McDougall, S, Katholm, J and Schukken, YH (2011) Molecular epidemiology of mastitis pathogens of dairy cattle and comparative relevance to humans. Journal of Mammary Gland Biology and Neoplasia 16, 357372.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Passe Pereira et al. supplementary material

Passe Pereira et al. supplementary material

Download Passe Pereira et al. supplementary material(PDF)
PDF 237.2 KB