Combined effects of intrinsic host gene (TRAPPC9) and extrinsic nutrient (folate) on resistance against S. aureus induced bovine mastitis

Abstract

Background: Drug-resistance and immunological escape of Staphylococcus aureus and its “superbug”, methicillin-resistant S. aureus (MRSA), have become one of main causes of bacterial infection in both human and animals. In dairy cattle, elimination of bovine mastitis induced by S. aureus is of importance because S. aureus-infected cows normally are culled passively. Methods: Here, we investigated the beneficial effects of bovine trafficking protein particle complex 9 (TRAPPC9) gene and folic acid supplementation in the control of mastitis induced by S. aureus or MRSA by a series of in vivo and in vitro experiments. Results: The data showed that the genetic mutations and DNA methylation of TRAPPC9 were highly linked with the mastitis resistance of dairy cows. Additionally, knockdown of bovine TRAPPC9 was significantly involved in the mRNA expression levels of interleukin’s genes (increased IL-1β and IL-6), and down-regulated the protein level of NF-κB-P65 in the mastitis cell model induced by MRSA. Meanwhile, dose-dependent folic acid addition can inhibit the invasion of MRSA into Mac-T cells and improve TRAPPC9 expression in dairy cows. Conclusions: Altogether, our data suggest that an appropriate dose of folic acid can significantly reduce the inflammation caused by MRSA partially through TRAPPC9 mediated NF-κB pathway. These findings provide new insights to control the drug-resistant pathogens and to restrict the overuse of antibiotics through combined effects of the intrinsic host gene and extrinsic nutrient.