Additional Simulation Results and Pharamacodynamic Concepts from Predicting drug resistance evolution: insights from antimicrobial peptides and antibiotics

Antibiotic resistance constitutes one of the most pressing public health concerns. Antimicrobial peptides (AMPs) of multicellular organisms are considered part of a solution to this problem, and AMPs produced by bacteria such as colistin are last-resort drugs. Importantly, AMPs differ from many antibiotics in their pharmacodynamic characteristics. Here we implement these differences within a theoretical framework to predict the evolution of resistance against AMPs and compare it to antibiotic resistance. Our analysis of resistance evolution finds that pharmacodynamic differences all combine to produce a much lower probability that resistance will evolve against AMPs. The finding can be generalized to all drugs with pharmacodynamics similar to AMPs. Pharmacodynamic concepts are familiar to most practitioners of medical microbiology, and data can be easily obtained for any drug or drug combination. Our theoretical and conceptual framework is, therefore, widely applicable and can help avoid resistance evolution if implemented in antibiotic stewardship schemes or the rational choice of new drug candidates

Construction of Functional Coatings with Durable and Broad-Spectrum Antibacterial Potential Based on Mussel-Inspired Dendritic Polyglycerol and in Situ-Formed Copper Nanoparticles

A novel surface coating with durable broad-spectrum antibacterial ability was prepared based on mussel-inspired dendritic polyglycerol (MI-dPG) embedded with copper nanoparticles (Cu NPs). The functional surface coating is fabricated via a facile dip-coating process followed by in situ reduction of copper ions with a MI-dPG coating to introduce Cu NPs into the coating matrix. This coating has been demonstrated to possess efficient long-term antibacterial properties against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and kanamycin-resistant E. coli through an “attract–kill–release” strategy. The synergistic antibacterial activity of the coating was shown by the combination of two functions of the contact killing, reactive oxygen species production and Cu ions released from the coating. Furthermore, this coating inhibited biofilm formation and showed good compatibility to eukaryotic cells. Thus, this newly developed Cu NP-incorporated MI-dPG surface coating may find potential application in the design of antimicrobial coating, such as implantable devices