RESUMO
The genus Mycobacterium is comprised of Gram-positive bacteria occupying a wide range of natural habitats and includes species that range from severe intracellular pathogens to economically useful and harmless microbes. The recent upsurge in the availability of microbial genome data has shown that genes encoding haemoglobin-like proteins are ubiquitous among Mycobacteria and that multiple haemoglobins (Hbs) of different classes may be present in pathogenic and non-pathogenic species. The occurrence of truncated haemoglobins (trHbs) and flavohaemoglobins (flavoHbs) showing distinct haem active site structures and ligand-binding properties suggests that these Hbs may be playing diverse functions in the cellular metabolism of Mycobacteria. TrHbs and flavoHbs from some of the severe human pathogens such as Mycobacterium tuberculosis and Mycobacterium leprae have been studied recently and their roles in effective detoxification of reactive nitrogen and oxygen species, electron cycling, modulation of redox state of the cell and facilitation of aerobic respiration have been proposed. This multiplicity in the function of Hbs may aid these pathogens to cope with various environmental stresses and survive during their intracellular regime. This chapter provides recent updates on genomic, structural and functional aspects of Mycobacterial Hbs to address their role in Mycobacteria.
Assuntos
Proteínas de Bactérias/metabolismo , Hemeproteínas/metabolismo , Mycobacterium/metabolismo , Hemoglobinas Truncadas/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Biotransformação , Hemeproteínas/química , Hemeproteínas/genética , Redes e Vias Metabólicas , Modelos Moleculares , Mycobacterium/química , Mycobacterium/genética , Óxido Nítrico/metabolismo , Óxido Nítrico/toxicidade , Oxirredução , Oxigênio/metabolismo , Oxigênio/toxicidade , Conformação Proteica , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Nitrogênio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/toxicidade , Hemoglobinas Truncadas/química , Hemoglobinas Truncadas/genéticaRESUMO
Tuberculosis and leprosy are among the most challenging infectious threats to human health. The ability of mycobacteria to persist in vivo in the presence of reactive nitrogen and oxygen species implies the presence in these bacteria of effective detoxification (pseudoenzymatic) systems. Mycobacterium tuberculosis and Mycobacterium leprae truncated hemoglobins (trHbs) belonging to group I (or N; trHbN) and group II (or O; trHbO) have recently been implicated in the scavenging of nitrogen monoxide (*NO) and peroxynitrite (ONOO-/HOONO). Furthermore, M. leprae trHbO was found to act as an efficient scavenger of the strong oxidant trioxocarbonate(*1-) (CO3*-) following the reaction of peroxynitrite with carbon dioxide (CO2). Here, mechanisms for scavenging of reactive nitrogen species by mycobacterial trHbs are reviewed, and detailed protocols for assessing pseudoenzymatic kinetics are provided.