Rajamanickam Karthic, Yang Jian, Chidambaram Saravana Babu, Sakharkar Meena Kishore
College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru-570015, Karnataka, India.
Animals (Basel). 2020 Nov 15;10(11):2117. doi: 10.3390/ani10112117.
Bovine mastitis is one of the major infectious diseases in dairy cattle, resulting in large economic loss due to decreased milk production and increased production cost to the dairy industry. Antibiotics are commonly used to prevent/treat bovine mastitis infections. However, increased antibiotic resistance and consumers' concern regarding antibiotic overuse make it prudent and urgent to develop novel therapeutic protocols for this disease.
Potential druggable targets were found in 20 mastitis-causing pathogens and conserved and unique targets were identified. Bacterial strains (ATCC 29213, and two clinical isolates CI 1 and CI 2) and (ATCC 12228, and two clinical isolates CI 1 and CI 2) were used in the present study for validation of an effective drug combination.
In the current study, we identified the common and the unique druggable targets for twenty mastitis-causing pathogens using an integrative approach. Furthermore, we showed that phosphorylcholine, a drug for a unique target gamma-hemolysin component B in , and ceftiofur, the mostly used veterinary antibiotic that is FDA approved for treating mastitis infections, exhibit a synergistic effect against and a strong additive effect against in vitro.
Based on the data generated in this study, we propose that combination therapy with drugs that work synergistically against conserved and unique targets can help increase efficacy and lower the usage of antibiotics for treating bacterial infections. However, these data need further validations in animal models of infection.
牛乳腺炎是奶牛的主要传染病之一，由于产奶量下降和乳制品行业生产成本增加，导致巨大的经济损失。抗生素通常用于预防/治疗牛乳腺炎感染。然而，抗生素耐药性的增加以及消费者对抗生素过度使用的担忧，使得开发针对这种疾病的新型治疗方案变得谨慎且紧迫。
在20种引起乳腺炎的病原体中发现了潜在的可成药靶点，并确定了保守和独特靶点。本研究使用细菌菌株（ATCC 29213以及两种临床分离株CI 1和CI 2）和（ATCC 12228以及两种临床分离株CI 1和CI 2）来验证有效的药物组合。
在当前研究中，我们使用综合方法确定了20种引起乳腺炎的病原体的常见和独特可成药靶点。此外，我们表明，磷酰胆碱（一种针对中的独特靶点γ-溶血素成分B的药物）和头孢噻呋（FDA批准用于治疗乳腺炎感染的最常用兽用抗生素）在体外对表现出协同作用，并对表现出强相加作用。
基于本研究产生的数据，我们提出针对保守和独特靶点协同作用的药物联合疗法有助于提高疗效并降低治疗细菌感染时抗生素的使用量。然而，这些数据需要在感染动物模型中进一步验证。
