Autoinducing Peptide-Mediated Bacterial Keratitis Therapy by Camouflaged <i>Staphylococcus aureus</i>.

Abstract

<i>Staphylococcus aureus</i> (<i>S. aureus</i>) is a prevalent and highly virulent pathogen responsible for microbial keratitis, which can lead to stromal damage, corneal perforation, and even blindness. In the postantibiotic era, the escalating prevalence of antibiotic-resistant <i>S. aureus</i> has rendered conventional antibiotic treatments increasingly ineffective, particularly due to autoinducing peptide-mediated signaling. Meanwhile, antibiotics disrupt the balance of the microbiota, which can further trigger ocular complications. To address these challenges, we designed and prepared a camouflaged bacterial system, supramolecular-coated <i>S. aureus</i> (SMCS), which can identify and aggregate with the matching pathogenic <i>S. aureus</i> through autoinducing peptide-mediated signaling. Upon the addition of amantadine, competitive host-guest interactions trigger the release of the antibacterial agent, enabling efficient and selective sterilization against pathogenic <i>S. aureus</i> with a fourfold higher efficacy than that against beneficial bacteria. In a rat model of bacterial keratitis, the proportion of <i>Staphylococcus</i> is 13.71% in the cornea after SMCS treatment, which is comparable to that in the healthy cornea (7.40%). SMCS+amantadine treatment can effectively eradicate bacteria, increase the diversity and abundance of corneal microorganisms, and preserve the balance of the corneal microbiota, providing promising clinical prospects in bacterial infection treatments and bacterial-mediated bioapplications.