Abstract
Simple SummaryTherapeutic success of bovine mastitis depends mainly on accurately diagnosing the type of pathogen involved. Despite the development prospects for bovine mastitis diagnosis, including new biomarker discovery to target specific pathogens with high sensitivity and specificity, treatment studies have shown controversial results, and the most efficient, safe, and economical treatments for mastitis are still topics of scientific debate. The goal of this research is the integration of different levels of systems biology data to predict candidate drugs for the control and management of E. coli mastitis. We propose that the novel drugs could be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines.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.
Highlights
IntroductionE. coli infection can cause either subclinical infection of the mammary gland or severe systemic disease
Clinical mastitis, an ongoing problem for dairy producers, results in considerable economic losses and has led to an increased risk of culling and death in dairy cows [1,2,3].Mastitis control programs targeting the prevalence of contagious mastitis pathogens have led to a reduction in the incidence of Staphylococcus aureus and Streptococcus agalactiae mastitis; as a result, environmental mastitis pathogens such as Escherichia coli (E. coli) have become the primary etiological agents of bovine mastitis on well-managed dairy farms [3,4,5,6].E. coli infection can cause either subclinical infection of the mammary gland or severe systemic disease
We used Heter-LP, a systems biology approach, to discover drugs to be repositioned for E. coli mastitis in the dairy cow by using different levels of biological data [22]
Summary
E. coli infection can cause either subclinical infection of the mammary gland or severe systemic disease. Untreated infections are often associated with significant economic damage due to the longer duration of infection, lower milk yield, and the potential for pathological changes to the mammary gland [3,10]. Successful therapeutic outcomes for bovine mastitis depend mainly on accurate diagnosis, the severity of udder pathology, drug selection, relevance of route of administration, supportive treatment, and elimination of predisposing factors. Despite the prospects for bovine mastitis diagnosis, including new biomarker discovery with high sensitivity and specificity to specific pathogens [3,11,12,13,14], the most efficient, safe, and economical treatments for mastitis are still topics of scientific debate [3,15,16].
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