Engineering Nanoparticle Antitoxins Utilizing Aromatic Interactions

Methicillin resistant Staphylococcus aureus (MRSA) is a highly virulent bacterium capable of inflicting severe infections. This pathogen has a long history of developing resistance to antibacterial drugs, and many phenotypes are capable of disabling the host immune response by releasing peptide and protein toxins with the capacity to lyse human polymorphonuclear neutrophils. The peptide phenol-soluble modulin α3 (PSMα3) has been identified as an important toxin released by the most virulent strains of MRSA. A library of polymer nonaparticles was synthesized by precipitation polymerization and screened for their ability to bind and neutralize this toxin. To generate high affinity, monomers were chosen to compliment the functional groups of PSMα3. Nanoparticles incorporating aromatic monomers provided a high affinity for the peptide and were effective at neutralizing its toxicity in vitro.