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 (<b>Mn-PTP</b>) was synthesized for the purpose of conducting synergistic therapy against mycobacterial infection. When subjected to white light irradiation, <b>Mn-PTP</b> generated multiple reactive species, including type I/II combined reactive oxygen species (ROS), carbon monoxide (CO), the toxic ligand <b>PTP</b>, and manganese oxides (MnO_<i>X</i>) with catalase-like ability. The antibacterial experiment demonstrated that irradiated <b>Mn-PTP</b> exhibited specific antibacterial effects on <i>Mycobacterium smegmatis</i> (<i>M. smegmatis</i>). It was found to cause damage to the bacterial membrane and effectively eradicate biofilms. Moreover, the in vivo experiment revealed that the photoactive <b>Mn-PTP</b> could promote the healing process of <i>M. smegmatis</i>-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.