Internalization, distribution, and activity of peptide H2 against the intracellular multidrug-resistant bovine mastitis-causing bacterium Staphylococcus aureus

• Published in: Scientific reports Vol. 9; no. 1; p. 7968
• Main Authors: Wang, Xiao, Teng, Da, Wang, Xiumin, Hao, Ya, Chen, Huixian, Mao, Ruoyu, Wang, Jianhua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.05.2019; Nature Publishing Group
• Subjects: 13; 13/31; 14/19; 14/28; 631/326/22; 631/80/2373; 64/60; Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antimicrobial Cationic Peptides - chemical synthesis; Antimicrobial Cationic Peptides - pharmacology; Cattle; Cell Line; Clathrin; Cytoplasm; Cytotoxicity; Drug Resistance, Multiple, Bacterial - drug effects; Endocytosis; Epithelial Cells - drug effects; Epithelial Cells - microbiology; Epithelial Cells - pathology; Female; Humanities and Social Sciences; Internalization; Intracellular; Lymphocytes; Lymphocytes T; Mammary gland; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - microbiology; Mammary Glands, Animal - pathology; Mastitis; Mastitis, Bovine - drug therapy; Mastitis, Bovine - microbiology; Mastitis, Bovine - pathology; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - growth & development; Methicillin-Resistant Staphylococcus aureus - pathogenicity; Mice; Microbial Sensitivity Tests; multidisciplinary; Multidrug resistance; Multidrug resistant organisms; Neutrophil Infiltration - drug effects; Peptides; Science; Science (multidisciplinary); Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcal Infections - veterinary; Staphylococcus aureus; Staphylococcus infections; Vancomycin; Vancomycin - pharmacology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-44459-x

Bovine mastitis is mainly caused by Staphylococcus aureus , which is difficult to eliminate, prone to escape from antibacterial agents, and may cause recurring infections due to the intracellular nature of its infection and multidrug resistance. In this study, the intracellular activities of the NZ2114 derivative peptide H18R (H2) against methicillin-resistant S. aureus (MRSA) and multidrug-resistant bovine S. aureus strains were investigated in bovine mammary epithelial MAC-T cells and mouse mammary glands. The minimum inhibitory concentrations of H2 against S. aureus were 0.5‒1 μg/ml; H2 displayed a lower cytotoxicity than its parental peptide NZ2114 (survival rates of MAC-T cells: 100% [H2 treatment] vs 60.7% [NZ2114 (256 μg/ml) treatment]). H2 was internalized into MAC-T cells mainly via clathrin-mediated endocytosis, and distributed in the cytoplasm. The intracellular inhibition rates against MRSA ATCC43300, the mastitis isolates S. aureus CVCC 3051 and E48 were above 99%, 99%, and 94%, respectively; these were higher than those in case of vancomycin (23–47%). In the mouse model of S. aureus E48-induced mastitis, after treatment with 100 μg of H2 and vancomycin, bacterial numbers in each mammary gland were reduced by 3.96- and 1.59-log CFU, respectively. Additionally, similar to NZ2114 and vancomycin, H2 alleviated the histopathological damage of the mammary tissue and polymorphonuclear neutrophil infiltration in the alveoli. These results suggest that H2 can be used as a safe and effective candidate for treating S. aureus -induced mastitis.