Copper-responsive liposomes for triggered cargo release employing a picolinamide-lipid conjugate.

In this work, we report triggered content release from liposomes brought about by copper chelation to a synthetic lipid switch containing a picolinamide headgroup. Fluorescence-based dye-leakage assays showcase release of carboxyfluorescein dye cargo upon copper treatment and control of liposomal release based on copper abundance. Our results additionally show that this platform is selective for copper and is accompanied by significant changes to liposome properties upon treatment with this ion.

A small molecule that inhibits the evolution of antibiotic resistance.

Antibiotic resistance rapidly develops against almost all available therapeutics. Therefore, searching for new antibiotics to overcome the problem of antibiotic resistance alone is insufficient. Given that antibiotic resistance can be driven by mutagenesis, an avenue for preventing it is the inhibition of mutagenic processes. We previously showed that the DNA translocase Mfd is mutagenic and accelerates antibiotic resistance development. Here, we present our discovery of a small molecule that inhibits Mfd-dependent mutagenesis, ARM-1 (anti-resistance molecule 1). We found ARM-1 using a high-throughput, small molecule, in vivo screen. Using biochemical assays, we characterized the mechanism by which ARM-1 inhibits Mfd. Critically, we found that ARM-1 reduces mutagenesis and significantly delays antibiotic resistance development across highly divergent bacterial pathogens. These results demonstrate that the mutagenic proteins accelerating evolution can be directly inhibited. Furthermore, our findings suggest that Mfd inhibition, alongside antibiotics, is a potentially effective approach for prevention of antibiotic resistance development during treatment of infections.