One-for-All Photoactivatable Manganese-Based Carbon Monoxide-Releasing Molecules (CORMs) for Synergistic Therapy of Mycobacterial Infection

Tuberculosis presents a severe threat to human health. It is of crucial importance to develop novel and effective treatments to combat mycobacterial infections, especially those caused by drug-resistant bacteria. In this study, a tricarbonyl manganese(I) complex (Mn-PTP) was synthesized for the purpose of conducting synergistic therapy against mycobacterial infection. When subjected to white light irradiation, Mn-PTP generated multiple reactive species, including type I/II combined reactive oxygen species (ROS), carbon monoxide (CO), the toxic ligand PTP, and manganese oxides (MnO_X) with catalase-like ability. The antibacterial experiment demonstrated that irradiated Mn-PTP exhibited specific antibacterial effects on Mycobacterium smegmatis (M. smegmatis). It was found to cause damage to the bacterial membrane and effectively eradicate biofilms. Moreover, the in vivo experiment revealed that the photoactive Mn-PTP could promote the healing process of M. smegmatis-infected skin wounds. This study pioneers innovative frameworks for developing one-for-all small-molecule pharmaceuticals capable of enabling synergistic therapeutic strategies against mycobacterial infections.