Preliminary study on gene regulation and its pathways in Chinese Holstein cows with clinical mastitis caused by Staphylococcus aureus

Wang, Wenjia; Li, Rongling; Ye, Tingzhu; Zhang, Xinxin; Chen, Chao; Liang, Ai-xin; Yang, Li-guo

doi:10.2478/jvetres-2022-0022

Abstract

Introduction

Clinical mastitis (CM) is one of the most common diseases of dairy cows globally, has a complex aetiology and recurs easily. Staphylococcus aureus is a frequently isolated pathogen responsible for bovine mastitis and remains difficult to eradicate.

Material and Methods

To characterise the transcriptional profiles of dairy cows infected by S. aureus, we performed an RNA-seq analysis of peripheral blood leukocytes in lactating Chinese Holstein dairy cows with CM and did the same with healthy cows’ samples as controls.

Results

A total of 4,286 genes were detected in the CM cases infected with S. aureus which were differentially expressed compared to the controls, 3,085 of which were upregulated, the remainder being downregulated. Notably, we observed that some differentially expressed genes (DEGs) had strong protein–protein interaction. Of these, six downregulated DEGs (AKR1C4, PTGS2, HNMT, EPHX2, CMBL, and IDH1) were involved in the metabolic pathway, while eight upregulated DEGs (VWF, GP9, MYLK, GP6, F2RL3, ITGB3, GP5, and PRKG1) were associated with the platelet activation pathway.

Conclusion

The transcriptome dataset of CM cases would be a valuable resource for clinical guidance on anti-inflammatory medication and for deeper understanding of the biological processes of CM response to S. aureus infection, and it would enable us to identify specific genes for diagnostic markers and possibly for targeted therapy.

References

Abebe R., Hatiya H., Abera M., Megersa B., Asmare K.: Bovine mastitis: prevalence, risk factors and isolation of Staphylococcus aureus in dairy herds at Hawassa milk shed, South Ethiopia. BMC Vet Res 2016, 12, 270, doi: 10.1186/s12917-016-0905-3.
Open DOI Search in Google Scholar Back to article
Araújo E.R., Sponchiado M., Pugliesi G., Van Hoeck V., Mesquita F.S., Membrive C.M., Binelli M.: Spatio-specific regulation of endocrine-responsive gene transcription by periovulatory endocrine profiles in the bovine reproductive tract. Reprod Fertil Dev 2014, 28, 1533–1544, doi: 10.1071/rd14178.
Open DOI Search in Google Scholar Back to article
Ayeni F.A., Gbarabon T., Andersen C., Norskov-Lauritsen N.: Comparison of identification and antimicrobial resistance pattern of Staphylococcus aureus isolated from Amassoma, Bayelsa state, Nigeria. Afr Health Sci 2015, 15, 1282–1288, doi: 10.4314/ahs.v15i4.30.
Open DOI Search in Google Scholar Back to article
Banos G., Bramis G., Bush S.J., Clark E.L., McCulloch M.E.B., Smith J., Schulze G., Arsenos G., Hume D.A., Psifidi A.: The genomic architecture of mastitis resistance in dairy sheep. BMC Genomics 2017, 18, 624, doi: 10.1186/s12864-017-3982-1.
Open DOI Search in Google Scholar Back to article
Barkema H.W., Schukken Y.H., Lam T.J., Beiboer M.L., Wilmink H., Benedictus G., Brand A.: Incidence of clinical mastitis in dairy herds grouped in three categories by bulk milk somatic cell counts. J Dairy Sci 1998, 81, 411–419, doi: 10.3168/jds.S0022-0302 (98)75591-2.
Open DOI Search in Google Scholar Back to article
Bolger A.M., Lohse M., Usadel B.: Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 2014, 30, 2114–2120, doi: 10.1093/bioinformatics/btu170.
Open DOI Search in Google Scholar Back to article
Bradford B.J., Yuan K., Farney J.K., Mamedova L.K., Carpenter A.J.: Invited review: Inflammation during the transition to lactation: New adventures with an old flame. J Dairy Sci 2015, 98, 6631–6650, doi: 10.3168/jds.2015-9683.
Open DOI Search in Google Scholar Back to article
Branco A., Yoshikawa F.S.Y., Pietrobon A.J., Sato M.N.: Role of Histamine in Modulating the Immune Response and Inflammation. Mediators Inflamm 2018, 9524075, doi: 10.1155/2018/9524075.
Open DOI Search in Google Scholar Back to article
Busso N., Chobaz-Péclat V., Hamilton J., Spee P., Wagtmann N., So A.: Essential role of platelet activation via protease activated receptor 4 in tissue factor-initiated inflammation. Arthritis Res Ther 2008, 10, R42, doi: 10.1186/ar2400.
Open DOI Search in Google Scholar Back to article
Cheng W.N., Han S.G.: Bovine mastitis: risk factors, therapeutic strategies, and alternative treatments - A review. Asian-Australas J Anim Sci 2020, 33, 1699–1713, doi: 10.5713/ajas.20.0156.
Open DOI Search in Google Scholar Back to article
Claes J., Vanassche T., Peetermans M., Liesenborghs L., Vandenbriele C., Vanhoorelbeke K., Missiakas D., Schneewind O., Hoylaerts M.F., Heying R., Verhamme P.: Adhesion of Staphylococcus aureus to the vessel wall under flow is mediated by von Willebrand factor-binding protein. Blood 2014, 124, 1669–1676, doi: 10.1182/blood-2014-02-558890.
Open DOI Search in Google Scholar Back to article
Dahl M.O., De Vries A., Galvão K.N., Maunsell F.P., Risco C.A., Hernandez J.A.: Combined effect of mastitis and parity on pregnancy loss in lactating Holstein cows. Theriogenology 2020, 143, 57–63, doi: 10.1016/j.theriogenology.2019.12.002.
Open DOI Search in Google Scholar Back to article
Dubois R.N., Abramson S.B., Crofford L., Gupta R.A., Simon L.S., Van De Putte L.B., Lipsky P.E.: Cyclooxygenase in biology and disease. FASEB J 1998, 12, 1063–1073.
Search in Google Scholar Back to article
Estevez B., Du X.: New Concepts and Mechanisms of Platelet Activation Signaling. Physiology 2017, 32, 162–177, doi: 10.1152/physiol.00020.2016.
Open DOI Search in Google Scholar Back to article
Hogan J., Gonzalez R., Harmon R., Nickerson S., Oliver S., Pankey J., Smith K.: Laboratory Field Handbook of Bovine Mastitis, National Mastitis Council, Madison, WI, 1999.
Search in Google Scholar Back to article
Jaeger A., Bardehle D., Oster M., Günther J., Muráni E., Ponsuksili S., Wimmers K., Kemper N.: Gene expression profiling of porcine mammary epithelial cells after challenge with Escherichia coli and Staphylococcus aureus in vitro. Vet Res 2015, 46, 50, doi: 10.1186/s13567-015-0178-z.
Open DOI Search in Google Scholar Back to article
Jamali H., Barkema H.W., Jacques M., Lavallée-Bourget E.M., Malouin F., Saini V., Stryhn H., Dufour S.: Invited review: Incidence, risk factors, and effects of clinical mastitis recurrence in dairy cows. J Dairy Sci 2018, 101, 4729–4746, doi: 10.3168/jds.2017-13730.
Open DOI Search in Google Scholar Back to article
Kawecki C., Lenting P.J., Denis C.V.: von Willebrand factor and inflammation. J Thromb Haemost 2017, 15, 1285–1294, doi: 10.1111/jth.13696.
Open DOI Search in Google Scholar Back to article
Kim D., Paggi J.M., Park C., Bennett C., Salzberg S.L.: Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol 2019, 37, 907–915, doi: 10.1038/s41587-019-0201-4.
Open DOI Search in Google Scholar Back to article
Kovaka S., Zimin A.V., Pertea G.M., Razaghi R., Salzberg S.L., Pertea M.: Transcriptome assembly from long-read RNA-seq alignments with StringTie2. Genome Biol 2019, 20, 278, doi: 10.1186/s13059-019-1910-1.
Open DOI Search in Google Scholar Back to article
Li Y., Yu G., Yuan S., Tan C., Lian P., Fu L., Hou Q., Xu B., Wang H.: Cigarette Smoke-Induced Pulmonary Inflammation and Autophagy Are Attenuated in Ephx2-Deficient Mice. Inflammation 2017, 40, 497–510, doi: 10.1007/s10753-016-0495-z.
Open DOI Search in Google Scholar Back to article
Love M.I., Huber W., Anders S.: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014, 15, 550, doi: 10.1186/s13059-014-0550-8.
Open DOI Search in Google Scholar Back to article
Motiño O., Francés D.E., Casanova N., Fuertes-Agudo M., Cucarella C., Flores J.M., Vallejo-Cremades M.T., Olmedilla L., Pérez Peña J., Bañares R., Boscá L., Casado M., Martín-Sanz P.: Protective Role of Hepatocyte Cyclooxygenase-2 Expression Against Liver Ischemia-Reperfusion Injury in Mice. Hepatology 2019, 70, 650–665, doi: 10.1002/hep.30241.
Open DOI Search in Google Scholar Back to article
Peetermans M., Meyers S., Liesenborghs L., Vanhoorelbeke K., De Meyer S.F., Vandenbriele C., Lox M., Hoylaerts M.F., Martinod K., Jacquemin M., Vanassche T., Verhamme P.: Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis. J Thromb Haemost 2020, 18, 722–731, doi: 10.1111/jth.14686.
Open DOI Search in Google Scholar Back to article
Robinson M.D., McCarthy D.J., Smyth G.K.: edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26, 139–140, doi: 10.1093/bioinformatics/btp616.
Open DOI Search in Google Scholar Back to article
Shannon P., Markiel A., Ozier O., Baliga N.S., Wang J.T., Ramage D., Amin N., Schwikowski B., Ideker T.: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003, 13, 2498–2504, doi: 10.1101/gr.1239303.
Open DOI Search in Google Scholar Back to article
Sharun K., Dhama K., Tiwari R., Gugjoo M.B., Iqbal Yatoo M., Patel S.K., Pathak M., Karthik K., Khurana S.K., Singh R., Puvvala B., Amarpal Singh R., Singh K.P., Chaicumpa W.: Advances in therapeutic and managemental approaches of bovine mastitis: a comprehensive review. Vet Q 2021, 41, 107–136, doi: 10.1080/01652176.2021.1882713.
Open DOI Search in Google Scholar Back to article
Shi L., Lv X., Liu L., Yang Y., Ma Z., Han B., Sun D.: A post-GWAS confirming effects of PRKG1 gene on milk fatty acids in a Chinese Holstein dairy population. BMC Genet 2019, 20, 53, doi: 10.1186/s12863-019-0755-7.
Open DOI Search in Google Scholar Back to article
Tong C., Chen Q., Zhao L., Ma J., Ibeagha-Awemu E.M., Zhao X.: Identification and characterization of long intergenic noncoding RNAs in bovine mammary glands. BMC Genomics 2017, 18, 468, doi: 10.1186/s12864-017-3858-4.
Open DOI Search in Google Scholar Back to article
Vanassche T., Kauskot A., Verhaegen J., Peetermans W.E., van Ryn J., Schneewind O., Hoylaerts M.F., Verhamme P.: Fibrin formation by staphylothrombin facilitates Staphylococcus aureus-induced platelet aggregation. Thromb Haemost 2012, 107, 1107–1121, doi: 10.1160/th11-12-0891.
Open DOI Search in Google Scholar Back to article
Wang D., Liu L., Augustino S.M.A., Duan T., Hall T.J., MacHugh D.E., Dou J., Zhang Y., Wang Y., Yu Y.: Identification of novel molecular markers of mastitis caused by Staphylococcus aureus using gene expression profiling in two consecutive generations of Chinese Holstein dairy cattle. J Anim Sci Biotechnol 2020, 11, 98, doi: 10.1186/s40104-020-00494-7.
Open DOI Search in Google Scholar Back to article
Wang X., Su F., Yu X., Geng N., Li L., Wang R., Zhang M., Liu J., Liu Y., Han B.: RNA-Seq Whole Transcriptome Analysis of Bovine Mammary Epithelial Cells in Response to Intracellular Staphylococcus aureus. Front Vet Sci 2020, 7, 642, doi: 10.3389/fvets.2020.00642.
Open DOI Search in Google Scholar Back to article
Xu T., Dong Z., Wang X., Qi S., Li X., Cheng R., Liu X., Zhang Y., Gao M.Q.: IL-1β induces increased tight junction permeability in bovine mammary epithelial cells via the IL-1β-ERK1/2-MLCK axis upon blood-milk barrier damage. J Cell Biochem 2018, 119, 9028–9041, doi: 10.1002/jcb.27160.
Open DOI Search in Google Scholar Back to article
Yoshikawa T., Nakamura T., Yanai K.: Histamine N-Methyltransferase in the Brain. Int J Mol Sci 2019, 20, 737, doi: 10.3390/ijms20030737.
Open DOI Search in Google Scholar Back to article
Zaatout N., Ayachi A., Kecha M.: Staphylococcus aureus persistence properties associated with bovine mastitis and alternative therapeutic modalities. J Appl Microbiol 2020, 129, 1102–1119, doi: 10.1111/jam.14706
Open DOI Search in Google Scholar Back to article