Protein lipidation is unique amongst post-translational modifications (PTMs) in enabling direct interaction with cell membranes, and is found in every form of life. Lipidation is important in normal function and in disease, but its intricate interplay with disease context presents a challenging for drug development. Global whole-proteome profiling of protein lipidation lies beyond the range of standard methods, but is well-suited to metabolic tagging with small 'clickable' chemical reporters that do not disrupt metabolism and function; chemoselective reactions are then used to add multifunctional labels exclusively to tagged-lipidated proteins. This chemical proteomic technology has opened up the first quantitative whole-proteome studies of the known major classes of protein lipidation, and the first insights into their full scope in vivo.
Pathogenic antibiotic resistant bacteria pose one of the most important health challenges of the 21st century. The overuse and abuse of antibiotics coupled with the natural evolutionary processes of bacteria has led to this crisis. Only incremental advances in antibiotic development have occurred over the last 30 years. Novel classes of molecules, such as engineered antibodies, antibiotic enhancers, siderophore conjugates, engineered phages, photo-switchable antibiotics, and genome editing facilitated by the CRISPR/Cas system, are providing new avenues to facilitate the development of antimicrobial therapies. The informatics revolution is transforming research and development efforts to discover novel antibiotics. The explosion of nanotechnology and micro-engineering is driving the invention of antimicrobial materials, enabling the cultivation of “uncultivable” microbes and creating specific and rapid diagnostic technologies. Finally, a revival in the ecological aspects of microbial disease management, the growth of prebiotics, and integrated management based on the “One Health” model, provide additional avenues to manage this health crisis. These, and future scientific and technological developments, must be coupled and aligned with sound policy and public awareness to address the risks posed by rising antibiotic resistance.