Evaluation of a Nisin-Eluting Nanofiber Scaffold To Treat Staphylococcus aureus-Induced Skin Infections in Mice

Abstract

Staphylococcus aureus is a virulent pathogen and a major causative agent of superficial and invasive skin and soft tissue infections (SSSTIs). Antibiotic resistance in S. aureus, among other bacterial pathogens, has rapidly increased, and this is placing an enormous burden on the health care sector and has serious implications for infected individuals, especially immunocompromised patients. Alternative treatments thus need to be explored to continue to successfully treat infections caused by S. aureus, including antibiotic-resistant strains of S. aureus. In this study, an antimicrobial nanofiber wound dressing was generated by electrospinning nisin (Nisaplin) into poly(ethylene oxide) and poly(D,L-lactide) (50:50) blend nanofibers. Active nisin diffused from the nanofiber wound dressings for at least 4 days in vitro, as shown by consecutive transfers onto plates seeded with strains of methicillin-resistant S. aureus (MRSA). The nisin-containing nanofiber wound dressings significantly reduced S. aureus Xen 36 bioluminescence in vivo and viable cell numbers in a murine excisional skin infection model. The bacterial burden of wounds treated with nisin-containing nanofiber wound dressings was 4.3 ؋ 10 2 CFU/wound, whereas wounds treated with control nanofiber wound dressings had 2.2 ؋ 10 7 CFU/wound on the last day of the trial (day 7). Furthermore, the wound dressings stimulated wound closure of excisional wounds, and no adverse effects were observed by histological analysis. Nisin-containing nanofiber wound dressings have the potential to treat S. aureus skin infections and to potentially accelerate wound healing of excisional wounds.

Efficacy of Lantibiotic Treatment of Staphylococcus aureus-Induced Skin Infections, Monitored byIn VivoBioluminescent Imaging

“…However, lantibiotics are effective in the treatment of S. aureus infections when administered via the subcutaneous, intraperitoneal, intranasal, and intravenous routes (11,12,29,30,47,48). Nisin incorporated into nanofibers could be used to treat topical S. aureus infections (14). Nisin-eluting nanofibers significantly reduced the bacterial load, as shown by bioluminescence and viable-cell counts, similar to the results of the current study.…”

“…Athymic nude mice do not display the same clinical severity of response to intradermal S. aureus infection as wild-type (BALB/c) mice, with clinical severity proposed to be driven by the inflammatory response to bacteria rather than the bacterial burden (25). However, in the current study, clinical severity measured by the rate of wound closure in superficial S. aureus-induced skin infections in athymic mice was similar to that reported for superficial S. aureus skin infection studies in wild-type (C57BL/6 or BALB/c) mice (4,14).…”

“…Amyloliquecidin is a two-component class II lantibiotic, with the individual peptides classified as mersacidin-like (␣-peptide) and LtnA2-like (␤-peptide) lantibiotics (24). Nisin is the prototypical lantibiotic and is active against several Gram-positive bacterial species, including antibiotic-resistant strains, and is effective in the treatment of microbial infections (13,14,(28)(29)(30). Clausin has not been studied to the same extent, with only a few studies investigating its activity and mode of action (31,32).…”

“…This response is unexpected, as nisin displays antimicrobial activity toward Gramnegative bacteria only when combined with a chelating agent or when the outer membrane has been damaged (20,21). In an unrelated study, Heunis and coworkers (14) observed accelerated wound healing when S. aureus-induced skin infections were treated with nisin incorporated into nanofibers. These studies imply that nisin, and possibly other lantibiotics, may have immunomodulatory activity that can be exploited to boost the immune system to combat infection and enhance wound healing.…”

“…Furthermore, certain lantibiotics, in addition to inhibiting cell wall biosynthesis, can form pores in the bacterial cell membrane, resulting in leakage of intracellular material (10). Several lantibiotics are active against antibiotic-resistant pathogens, and their efficacy in treating bacterial infections has been reported in several animal models (11)(12)(13)(14).…”