Abstract
Simple Summary The high incidence of stress-associated diseases post rabbit weaning results in great losses threatening the rabbit industry. The increasing emergence of multidrug resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) causes life threatening infections worldwide. Thus, the necessity to look inward for natural alternative treatments is now compelling. In this perspective, Nigella sativa extract (NSE) could serve as an effective antibiotic alternate source against MRSA. Herein, NSE was found to possess iin vitro antimicrobial activities against MRSA clinical isolates. Moreover, the synergistic activity between NSE and other antimicrobials was employed to overcome the MRSA resistance. Our findings added new insights for application of NSE in diets of growing rabbits as a growth promoting and an immunostimulant agent, which in turn reduced the high risk associated MRSA infections in growing rabbits. Weaning is the most crucial period associated with increased stress and susceptibility to diseases in rabbits. Methicillin-resistant Staphylococcus aureus (MRSA), a historic emergent pathogen related to post weaning stressors, adversely affects rabbit's growth rate and productive cycle. Since MRSA is rapidly evolving antibiotics resistance, natural products are desperately required to tackle the public health threats posed by antimicrobial resistance. Thus, this study aimed to screen the iin vitro antibacterial activity of Nigella sativa extract (NSE) and its interactions with antibiotics against MRSA isolates. Moreover, 200 weaned rabbits were divided into 4 groups to investigate the iin vivo superiority of NSE graded levels towards growth performance, tight junction integrity, immune responsiveness and resistance against MRSA. Herein, NSE showed promising antimicrobial activities against MRSA isolates from animal (77.8%) and human (64.3%) origins. Additionally, MRSA isolates exposed to NSE became sensitive to all antimicrobials to which they were previously resistant. Our results described that the growth-promoting functions of NSE, especially at higher levels, were supported by elevated activities of digestive linked enzymes. Post-NSE feeding, rabbits' sera mediated bactericidal activities against MRSA. Notably, upregulated expression of occludin, CLDN-1, MUC-2 and JAM-2 genes was noted post NSE supplementation with maximum transcriptional levels in 500 mg/kg NSE fed group. Our data described that NSE constitutively motivated rabbits' immune responses and protected them against MRSA-induced experimental infection. Our results suggest the antimicrobial, growth stimulating and immunomodulation activities of NSE to maximize the capability of rabbits for disease response.