Gallium Hematoporphyrin inhibits Mycobacteroides abscessus in vitro, including biofilm formation and stability

Abstract

The nontuberculous mycobacterial (NTM) pathogen, Mycobacteroides abscessus, can cause severe pulmonary infections. Emerging multidrug resistance to current antibiotics poses significant challenges for treatment of M. abscessus infections. Thus, new antibiotics are needed, preferably ones that target new microbial pathways. Earlier, we examined the in vitro inhibitory activities of several gallium compounds, Ga(NO₃)₃, GaCl₃, gallium meso-tetraphenylporphyrin (GaTP) and gallium nanoparticles (GaNP), against intra- and extracellular M. abscessus. We have previously shown that these gallium compounds function by disrupting microbial iron/heme acquisition and utilization. Here, we explored an alternative therapeutic approach using gallium hematoporphyrin (GaHP), a toxic heme analogue. GaHP inhibited growth of clinical M. abscessus isolates, with MICs in range of 0.5 and 1 μg/ml. GaHP was more active than rifampin against M. abscessus, showed synergism with clarithromycin, and induced ROS formation in M. abscessus. GaHP also inhibited biofilm formation of both smooth and rough M. abscessus colony morphotypes. GaHP also disrupted preformed biofilms by both M. abscessus morphotypes. Hence, GaHP could be a potential lead compound for development of anti-NTM agents that targets heme-metabolism of M. abscessus.