Five-In-One Antibacterial Strategy: A Mn(I) Complex Lights Up the Fight Against Tuberculosis

Abstract

Tuberculosis, which the WHO describes as the "world's top infectious killer," demands novel combating strategies rather than conventional ones, as the situation of Mycobacterium tuberculosis (Mtb) resistance to therapeutic drugs is continuous, leading to millions of deaths each year. In a recent study, Lai et al. report a manganese(I)-based photoactivatable carbon monoxide-releasing molecule (Mn-PTP) that unifies photodynamic therapy, transition metal reactivity, and carbon monoxide (CO) delivery into a single light-activated therapeutic platform. Upon white-light irradiation, Mn-PTP releases CO, generates both type I and type II reactive oxygen species (ROS), liberates a toxic antibacterial ligand (PTP), and forms catalytically active manganese oxides (MnO_x) species that decompose intracellular hydrogen peroxide (H₂O₂), thereby alleviating hypoxia and amplifying ROS generation. Mn-PTP demonstrates high selectivity for Mycobacterium smegmatis with, potent in vitro antibacterial activity (MIC₉₀ = 3.11 μM), robust biofilm disruption of M. smegmatis, and minimal cytotoxicity to normal cells. In in vivo, the compound significantly accelerates wound healing in infected mice, outperforming isoniazid. This highlight discusses Mn-PTP as a powerful "one-for-all" agent which, upon irradiation, releases five key components that, much like the five fingers through coordinated action, form a fist that effectively combats and eliminates bacterial infections, offering a powerful blueprint for next-generation metal-based therapeutics against persistent mycobacterial infections.

Keywords: bioinorganic chemistry; gas therapy; photoactivated antibacterial agents; photodynamic chemistry; tuberculosis therapy.