Effective Antimicrobial Activity of Plectasin-Derived Antimicrobial Peptides against Staphylococcus aureus Infection in Mammary Glands

Abstract

Staphylococcus aureus (S. aureus) is the causative agent for a wide variety of illnesses ranging from minor skin infections to life-threatening diseases. Development of antibiotic resistance by the bacteria has rendered many antibiotics ineffective. It has been known that plectasin-derived antimicrobial peptides (AMPs; NZ2114 and MP1102) are promising alternatives to antibiotics. However, their activities against S. aureus in mammary glands were unknown. Our objective was to assess the antimicrobial activities of NZ2114 and MP1102 against S. aureus in milk, in cultured mammary epithelial cells, and in a mouse model in order to evaluate their potentials as anti-mastitis agents. NZ2114 and MP1102 showed in vitro bactericidal effects against S. aureus in both the culture medium and the milk. NZ2114 and MP1102 at the concentration of 100 μg/mL reduced the number of S. aureus by almost 100% within 4 h in processed bovine milk. Similarly, both NZ2114 and MP1102 were efficient to reduce the number of internalized S. aureus in cultured mammary epithelial cells. Finally, both AMPs significantly reduced the S. aureus load and concentrations of TNF-α and IL-6 in mammary glands, compared to a buffer control in the mouse model. Our results suggest that NZ2114 and MP1102 may be used to treat S. aureus-induced mastitis.

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

“…Additionally, after treatment with the peptides or vancomycin, polymorphonuclear neutrophils disappeared from the alveoli (Fig. 7), which is consistent with the findings from previous studies 23 . It was also observed that the peptides NZ2114/H2 and vancomycin can protect the mammary glands of the mice from S. aureus infection.…”

“…It has been demonstrated that polyhexamethylene biguanide, plectasin, NZ2114, and MP1102 have a high efficiency against intracellular S. aureus in keratinocytes, human THP-1 and mouse RAW264.7 macrophages 17,21,22,33 . The bovine mammary epithelial MAC-T cells have been widely used to study the physiological function of breast tissues, screen for effective drugs, and simulate the actual conditions of bovine mastitis 23 . The results of this study showed that H2 displayed a strong ability to kill the three different internalized S. aureus strains in MAC-T cells, which was equal to that of NZ2114, but superior to that of vancomycin (Fig.…”

“…6). The lower efficiency of vancomycin in vivo may be associated with the presence of body fluids such as milk and serum, which may reduce the antibacterial activity of drugs 23 . Additionally, after treatment with the peptides or vancomycin, polymorphonuclear neutrophils disappeared from the alveoli (Fig.…”

“…Both NZ2114 (D9N, M13L, and Q14R) and MP1102 (D9Q, M13V, and Q14R), which are derivatives of plectasin, have a stronger activity than their parent; this may be due to their more positive net charges and higher hydrophobicity 17–20 . Additionally, similar to daptomycin and vancomycin, NZ2114 and MP1102 display a potent intracellular activity against S. aureus in THP-1 monocytes 21 , RAW 264.7 macrophages 22 , and mammary epithelial cells 23 , and can reduce the S. aureus load in the mammary glands of mice 23 . However, NZ2114 and MP1102 are more toxic towards mouse macrophages than vancomycin due to their high hydrophobicity 22 .…”

Overview of Host Defense Peptides and Their Applications for Plastic and Reconstructive Surgeons

“…[109][110][111] While commercial development was halted, preclinical studies are actively ongoing with promising results. [112][113][114][115][116] Oragenics (Tampa, FL, USA) has investigated…”