Carbon monoxide releasing molecules as antibacterial agents: antibacterial mechanisms, design principles, and controlled methods

One of the challenges in antibiotic therapy is the development of bacterial resistance. It is urgent to develop new alternative antibacterial treatment strategies. Recently, researchers have paid close attention to carbon monoxide (CO) therapy, which can kill bacteria even in biofilms effectively, without drug resistance. The key to CO antibacterial activity lies in identifying carbon monoxide releasing molecules (CORMs) to achieve targeted delivery and controlled release. In this review, we elucidate the antibacterial mechanisms and design principles of CORMs. Furthermore, methods for controlled release and detection of CO are also summarized. CORMs enter bacterial cells, release CO inside the cells to inhibit bacterial respiration, and simultaneously interfere with bacterial metabolism and overall physiological functions. The integration of CO or CORMs with macromolecules or nanomaterials has improved the stability and release duration of CO delivery, to some extent achieving targeted delivery and enhancing biological safety. This review will provide guidance for the design and synthesis of new CORMs, which will promote the clinical therapy of CO.