Abstract
Antibiotic resistance and the shortage of novel antimicrobials are among the biggest challenges facing society. One of the major factors contributing to resistance is the use of frontline clinical antibiotics in veterinary practice. In order to properly manage dwindling antibiotic resources, we must identify antimicrobials that are specifically targeted to veterinary applications. Nisin is a member of the lantibiotic family of antimicrobial peptides that exhibit potent antibacterial activity against many gram-positive bacteria, including human and animal pathogens such as Staphylococcus, Bacillus, Listeria, and Clostridium. Although not currently used in human medicine, nisin is already employed commercially as an anti-mastitis product in the veterinary field. Recently we have used bioengineering strategies to enhance the activity of nisin against several high profile targets, including multi-drug resistant clinical pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) and also against staphylococci and streptococci associated with bovine mastitis. However, newly emerging pathogens such as methicillin resistant Staphylococcus pseudintermedius (MRSP) pose a significant threat in terms of veterinary health and as a reservoir for antibiotic resistance determinants. In this study we created a nisin derivative with enhanced antimicrobial activity against S. pseudintermedius. In addition, the novel nisin derivative exhibits an enhanced ability to impair biofilm formation and to reduce the density of established biofilms. The activities of this peptide represent a significant improvement over that of the wild-type nisin peptide and merit further investigation with a view to their use to treat S. pseudintermedius infections.
Highlights
The diminished capacity of currently available antibiotics to control pathogenic bacteria is a major cause for concern
As the emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) is most likely linked to selective pressure from antimicrobials, more stringent limitations on their use in companion animals may become a reality
Research into the most advantageous treatment strategies for existing antimicrobial agents as well as alternatives to conventional therapy is urgently required. Due to their many unique properties, the lantibiotic class of bacteriocins would seem to have the potential to breach the gap between effective antibiosis and increasingly drug-resistant clinical and veterinary microbes
Summary
The diminished capacity of currently available antibiotics to control pathogenic bacteria is a major cause for concern. Against this backdrop, methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged over the last decade as a critically important, opportunistic canine pathogen responsible for skin, soft tissue, and surgical site infections [1]. Frequently detected in dogs, MRSP has been isolated from several other host species.
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