A Polycation Antimicrobial Peptide Mimic without Resistance Buildup against Propionibacterium Acnes.

A preliminary study is reported for a polycation antimicrobial peptide (AMP) mimic against Propionibacterium acnes, which is associated with acne vulgaris, a common skin condition. Antibiotics are commonly used against P. acnes but buildup of resistance is well-known. Worse, antibiotic regimens build up resistance for more sensitive bacteria such as Staphylococcus epidermidis. The polycation AMP mimic C12-50, 1, is chosen for the present study as it has been previously shown to have high antimicrobial effectiveness. This study reports that C12-50 is active against P. acnes (strain ATCC 6919) with a minimum inhibitory concentration (MIC) of 6.3 µg mL-1 . To monitor resistance build-up ten passages are conducted with C12-50 against P. acnes. The MIC remains constant with no resistance buildup. Parallel studies with erythromycin confirm previously reported resistance buildup. The results point to a promising pathway to applications for polycation AMP mimics against P. acnes.

Real-Time Observation of Antimicrobial Polycation Effects on Escherichia coli: Adapting the Carpet Model for Membrane Disruption to Quaternary Copolyoxetanes.

Real-time atomic force microscopy (AFM) was used for analyzing effects of the antimicrobial polycation copolyoxetane P[(C12)-(ME2Ox)-50/50], C12-50 on the membrane of a model bacterium, Escherichia coli (ATCC# 35218). AFM imaging showed cell membrane changes with increasing C12-50 concentration and time including nanopore formation and bulges associated with outer bacterial membrane disruption. A macroscale bactericidal concentration study for C12-50 showed a 4 log kill at 15 µg/mL with conditions paralleling imaging (1 h, 1x PBS, physiological pH, 25 °C). The dramatic changes from the control image to 1 h after introducing 15 µg/mL C12-50 are therefore reasonably attributed to cell death. At the highest concentration (60 µg/mL) further cell membrane disruption results in leakage of cytoplasm driven by detergent-like action. The sequence of processes for initial membrane disruption by the synthetic polycation C12-50 follows the carpet model posited for antimicrobial peptides (AMPs). However, the nanoscale details are distinctly different as C12-50 is a synthetic, water-soluble copolycation that is best modeled as a random coil. In a complementary AFM study, chemical force microscopy shows that incubating cells with C12-50 decreased the hydrophobicity across the entire cell surface at an early stage. This finding provides additional evidence indicating that C12-50 polycations initially bind with the cell membrane in a carpet-like fashion. Taken together, real time AFM imaging elucidates the mechanism of antimicrobial action for copolyoxetane C12-50 at the single cell level. In future work this approach will provide important insights into structure-property relationships and improved antimicrobial effectiveness for synthetic amphiphilic polycations.

Competition between Ultrafast Energy Flow and Electron Transfer in a Ru(II)-Loaded Polyfluorene Light-Harvesting Polymer.

This Letter describes the synthesis and photophysical characterization of a Ru(II) assembly consisting of metal polypyridyl complexes linked together by a polyfluorene scaffold. Unlike many scaffolds incorporating saturated linkages, the conjugated polymer in this system acts as a functional light-harvesting component. Conformational disorder breaks the conjugation in the polymer backbone, resulting in a chain composed of many chromophore units, whose relative energies depend on the segment lengths. Photoexcitation of the polyfluorene by a femtosecond laser pulse results in the excitation of polyfluorene, which then undergoes direct energy transfer to the pendant Ru(II) complexes, producing Ru(II)* excited states within 500 fs after photoexcitation. Femtosecond transient absorption data show the presence of electron transfer from PF* to Ru(II) to form charge-separated (CS) products within 1-2 ps. The decay of the oxidized and reduced products, PF(+•) and Ru(I), through back electron transfer are followed using picosecond transient absorption methods.