Truncated hemoglobin HbN protects Mycobacterium bovis from nitric oxide

AUTOR(ES)

Ouellet, Hugues

FONTE

The National Academy of Sciences

RESUMO

Mycobacterium tuberculosis, the causative agent of human tuberculosis, and Mycobacterium bovis each express two genes, glbN and glbO, encoding distantly related truncated hemoglobins (trHbs), trHbN and trHbO, respectively. Here we report that disruption of M. bovis bacillus Calmette–Guérin glbN caused a dramatic reduction in the NO-consuming activity of stationary phase cells, and that activity could be restored fully by complementing knockout cells with glbN. Aerobic respiration of knockout cells was inhibited markedly by NO in comparison to that of wild-type cells, indicating a protective function for trHbN. TyrB10, which is highly conserved in trHbs and interacts with the bound oxygen, was found essential for NO consumption. Titration of oxygenated trHbN (trHbN⋅O2) with NO resulted in stoichiometric oxidation of the protein with nitrate as the major product of the reaction. The second-order rate constant for the reaction between trHbN⋅O2 and NO at 23°C was 745 μM−1⋅s−1, demonstrating that trHbN detoxifies NO 20-fold more rapidly than myoglobin. These results establish a role for a trHb and demonstrate an NO-metabolizing activity in M. tuberculosis or M. bovis. trHbN thus might play an important role in persistence of mycobacterial infection by virtue of trHbN′s ability to detoxify NO.

Documentos Relacionados

• Role of Pre-A Motif in Nitric Oxide Scavenging by Truncated Hemoglobin, HbN, of Mycobacterium tuberculosis*S⃞
• Theoretical Investigations of Nitric Oxide Channeling in Mycobacterium tuberculosis Truncated Hemoglobin N
• Mechanism of nitric oxide-dependent killing of Mycobacterium bovis BCG in human alveolar macrophages.
• Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.
• Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity