Peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin O

During infection, Mycobacterium leprae is faced with the host macrophagic environment limiting the growth of the bacilli. However, (pseudo-)enzymatic detoxification systems, including truncated hemoglobin O (Ml-trHbO), could allow this mycobacterium to persist in vivo. Here, kinetics of peroxynitrite (ONOOH/ONOO−) detoxification by ferryl Ml-trHbO (Ml-trHbOFe(IV)O), obtained by treatment with H2O2, is reported. Values of the second-order rate constant for peroxynitrite detoxification by Ml-trHbOFe(IV)O (i.e., of Ml-trHbOFe(III) formation; kon), at pH 7.2 and 22.0 °C, are 1.5 × 104 M−1 s−1, and 2.2 × 104 M−1 s−1, in the absence of and presence of physiological levels of CO2 (∼1.2 × 10−3 M), respectively. Values of kon increase on decreasing pH with a pKa value of 6.7, this suggests that ONOOH reacts preferentially with Ml-trHbOFe(IV)O. In turn, peroxynitrite acts as an antioxidant of Ml-trHbOFe(IV)O, which could be responsible for the oxidative damage of the mycobacterium. As a whole, Ml-trHbO can undertake within the same cycle H2O2 and peroxynitrite detoxification.