Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec 23;12(1):29.
doi: 10.3390/ani12010029.

Systems Biology-Derived Genetic Signatures of Mastitis in Dairy Cattle: A New Avenue for Drug Repurposing

Somayeh Sharifi  1   2 , Maryam Lotfi Shahreza  3 , Abbas Pakdel  1 , James M Reecy  2 , Nasser Ghadiri  4 , Hadi Atashi  5 , Mahmood Motamedi  6 , Esmaeil Ebrahimie  7   8   9
Affiliations

Systems Biology-Derived Genetic Signatures of Mastitis in Dairy Cattle: A New Avenue for Drug Repurposing

Somayeh Sharifi et al. Animals (Basel). .

Abstract

Mastitis, a disease with high incidence worldwide, is the most prevalent and costly disease in the dairy industry. Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the leading agents causing acute severe infection with clinical signs. E. Coli, environmental mastitis pathogens, are the primary etiological agents of bovine mastitis in well-managed dairy farms. Response to E. Coli infection has a complex pattern affected by genetic and environmental parameters. On the other hand, the efficacy of antibiotics and/or anti-inflammatory treatment in E. coli mastitis is still a topic of scientific debate, and studies on the treatment of clinical cases show conflicting results. Unraveling the bio-signature of mastitis in dairy cattle can open new avenues for drug repurposing. In the current research, a novel, semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration, was used to potentially identify novel therapeutic avenues for the treatment of E. coli mastitis. Online data repositories relevant to known diseases, drugs, and gene targets, along with other specialized biological information for E. coli mastitis, including critical genes with robust bio-signatures, drugs, and related disorders, were used as input data for analysis with the Heter-LP algorithm. Our research identified novel drugs such as Glibenclamide, Ipratropium, Salbutamol, and Carbidopa as possible therapeutics that could be used against E. coli mastitis. Predicted relationships can be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines or a combination of two or more active compounds to treat this infectious disease.

Keywords: E. coli; drug repositioning; drug targets; gene regulation; inflammation; mastitis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The workflow for this research. (a) Data related to diseases, drugs, and their targets gathered from different data sources (Table 1). (b) Key genes with robust bio-signatures and key regulatory effects in response to E. coli (Table 2). (c) Diseases or biological processes functionally related to mastitis identified by using the Pathway Studio web tool (Figure 2). (d) Drugs and antibiotics relevant to E. coli mastitis gathered by literature mining (Table 3). (e) A suitable heterogeneous network constructed by integration of data from parts A, B, C, D (f) Running the Heter-LP algorithm on the constructed network to predict important relations involved in mastitis (described in Section 2.2). (g) Predicted drugs, ranked according to their score computed by Heter-LP (Table 4 and Supplementary Table S2).
Figure 2
Figure 2
Disease network related to mastitis constructed by using Pathway Studio web tool (based on at least two references).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Rollin E., Dhuyvetter K.C., Overton M.W. The cost of clinical mastitis in the first 30 days of lactation: An economic modeling tool. Prev. Vet. Med. 2015;122:257–264. doi: 10.1016/j.prevetmed.2015.11.006. - DOI - PubMed
    1. Bar D., Tauer L.W., Bennett G., González R.N., Hertl J.A., Schukken Y.H., Schulte H.F., Welcome F.L., Gröhn Y.T. The cost of generic clinical mastitis in dairy cows as estimated by using dynamic programming. J. Dairy Sci. 2008;91:2205–2214. doi: 10.3168/jds.2007-0573. - DOI - PubMed
    1. Sharifi S., Pakdel A. Mastitis Symptoms, Triggers and Treatment. NOVA; New York, NY, USA: 2019. Bovine Mastitis: Etiology and Epidemiology, challenges, current trends and future perspectives in monitoring, detection and treatment.
    1. Bradley A. Bovine mastitis: An evolving disease. Vet. J. 2002;164:116–128. doi: 10.1053/tvjl.2002.0724. - DOI - PubMed
    1. Hogan J., Larry Smith K. Coliform mastitis. Vet. Res. 2003;34:507–519. doi: 10.1051/vetres:2003022. - DOI - PubMed
-