Date of Presentation
5-2-2024 12:00 AM
College
Rowan-Virtua School of Osteopathic Medicine
Poster Abstract
Staphylococcus aureus is an opportunistic pathogen that lives on surfaces and skin and can cause serious infections once inside the body. While antibiotics effectively kill bacteria, there are a growing number of infections with antibiotic-resistant strains. Antimicrobial peptides (AMPs) are part of the innate immune system and can eliminate pathogens including bacteria, fungi, and viruses, and are a promising alternative to antibiotics. Although studies have reported that AMP-functionalized hydrogels can prevent bacterial adhesion and biofilm formation, these materials generally consist of one AMP at an arbitrary concentration, and AMP dosing and the combined effects of multiple AMPs are not well understood. Here, three AMPs with different antibacterial properties were synthesized and the soluble minimum inhibitory concentrations (MICs) of each AMP against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) determined. Hydrogels with immobilized AMPs at their MIC (DD13RIP 27.5 µM; indolicidin 43.8 µM; P10 120 µM) were effective in preventing MRSA adhesion and biofilm formation. Checkerboard array screens identified synergy between indolicidin (3.125 µM) and P10 (12.5 µM) based on soluble fractional inhibitory concentrations (FICs) against MRSA, and hydrogels formed with these AMPs at half of their synergistic FICs (total peptide concentration, 8.5 µM) were highly efficacious in killing MRSA. Mammalian cells cultured atop these hydrogels are also highly viable, demonstrating that the AMP hydrogels developed are biocompatible and selectively eradicate bacteria based on soluble checkerboard screening data.
Keywords
Antimicrobial peptides, AMP screening, Hydrogels, Thiol-norbornene, Medical-device infections, Bacterial Adhesion, Biofilms, Bacterial Infections, Cross Infection
Disciplines
Amino Acids, Peptides, and Proteins | Bacterial Infections and Mycoses | Biological Factors | Chemical and Pharmacologic Phenomena | Clinical Epidemiology | Investigative Techniques | Medicine and Health Sciences | Patient Safety
Document Type
Poster
Included in
Amino Acids, Peptides, and Proteins Commons, Bacterial Infections and Mycoses Commons, Biological Factors Commons, Chemical and Pharmacologic Phenomena Commons, Clinical Epidemiology Commons, Investigative Techniques Commons, Patient Safety Commons
Soluble Antimicrobial Peptide (AMP) Screening to Rationally Design AMP-Hydrogels that Selectively Prevent Biofilm Formation
Staphylococcus aureus is an opportunistic pathogen that lives on surfaces and skin and can cause serious infections once inside the body. While antibiotics effectively kill bacteria, there are a growing number of infections with antibiotic-resistant strains. Antimicrobial peptides (AMPs) are part of the innate immune system and can eliminate pathogens including bacteria, fungi, and viruses, and are a promising alternative to antibiotics. Although studies have reported that AMP-functionalized hydrogels can prevent bacterial adhesion and biofilm formation, these materials generally consist of one AMP at an arbitrary concentration, and AMP dosing and the combined effects of multiple AMPs are not well understood. Here, three AMPs with different antibacterial properties were synthesized and the soluble minimum inhibitory concentrations (MICs) of each AMP against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) determined. Hydrogels with immobilized AMPs at their MIC (DD13RIP 27.5 µM; indolicidin 43.8 µM; P10 120 µM) were effective in preventing MRSA adhesion and biofilm formation. Checkerboard array screens identified synergy between indolicidin (3.125 µM) and P10 (12.5 µM) based on soluble fractional inhibitory concentrations (FICs) against MRSA, and hydrogels formed with these AMPs at half of their synergistic FICs (total peptide concentration, 8.5 µM) were highly efficacious in killing MRSA. Mammalian cells cultured atop these hydrogels are also highly viable, demonstrating that the AMP hydrogels developed are biocompatible and selectively eradicate bacteria based on soluble checkerboard screening data.