Iron sulfur cluster proteins and microbial regulation: implications for understanding tuberculosis

All pathogenic and nonpathogenic microbes are continuously exposed to environmental or endogenous reactive oxygen and nitrogen species, which can critically effect survival and disease. Iron–sulfur [Fe–S] cluster containing prosthetic groups provide the microbial cell with a unique capacity to sense and transcriptionally respond to diatomic gases (e.g. NO and O2) and redox-cycling agents. Recent advances in our understanding of the mechanisms for how the FNR and SoxR [Fe–S] cluster proteins respond to NO and O2 have provided new insights into the biochemical mechanism of action of the Mycobacterium tuberculosis (Mtb) family of WhiB [Fe–S] cluster proteins. These insights have provided the basis for establishing a unifying paradigm for the Mtb WhiB family of proteins. Mtb is the etiological agent for tuberculosis (TB), a disease that affects nearly one-third of the world's population.

► The repertoire of Fe–S cluster harboring proteins inmycobacterial species was examined. ► Mtb contains around 50 Fe–S cluster proteins, which is about half of thatof E. coli. ► Notably, the number of 4Fe–4S clusters motifs in Mtb correlates with that of anaerobic microbes. ► The role of WhiB proteins in mycobacterial physiology, virulence and disease was discussed.