Lysostaphin-functionalized cellulose fibers with antistaphylococcal activity for wound healing applications

Abstract

With the emergence of “super bacteria” that are resistant to antibiotics, e.g., methicillin-resistant Staphylococcus aureus, novel antimicrobial therapies are needed to prevent associated hospitalizations and deaths. Bacteriophages and bacteria use cell lytic enzymes to kill host or competing bacteria, respectively, in natural environments. Taking inspiration from nature, we have employed a cell lytic enzyme, lysostaphin (Lst), with specific bactericidal activity against S. aureus, to generate anti-infective bandages. Lst was immobilized onto biocompatible fibers generated by electrospinning homogeneous solutions of cellulose, cellulose-chitosan, and cellulose-poly(methylmethacrylate) (PMMA) from 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc]), room temperature ionic liquid. Electron microscopic analysis shows that these fibers have submicron-scale diameter. The fibers were chemically treated to generate aldehyde groups for the covalent immobilization of Lst. The resulting Lst-functionalized cellulose fibers were processed to obtain bandage preparations that showed activity against S. aureus in an in vitro skin model with low toxicity toward keratinocytes, suggesting good biocompatibility for these materials as antimicrobial matrices in wound healing applications.