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Antioxid Redox Signal.
April 11,2012.[Article in press]

Environmental heme-based sensor proteins: Implications for understanding bacterial pathogenesis.

Farhana A, Saini V, Kumar A, Lancaster J, Steyn AJ.

University of Alabama at Birmingham, Microbiology, Birmingham, Alabama, United States.


Significance: Heme is an important prosthetic group required in wide array of functions including respiration, photosynthesis, metabolism, O<sub>2</sub> transport, xenobiotic detoxification, and peroxide production and destruction, and is an essential cofactor in proteins such as catalases, peroxidases and members of the cytochrome P450 superfamily. Importantly, bacterial heme-based sensor proteins exploit the redox chemistry of heme to sense environmental gases and the intracellular redox state of the cell. Recent Advances: The bacterial proteins FixL (<i>Rhizobium ssp.</i>), CooA (<i>Rhodospirillum rubrum</i>), EcDos (<i>E. coli</i>), RcoM (<i>Burkholderia xenovorans</i>) and particularly <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) DosS and DosT have emerged as model paradigms of environmental heme-based sensors capable of detecting multiple gases including NO, CO and O<sub>2</sub>. Critical issues: How the diatomic gases NO, CO or O<sub>2</sub> bind to heme iron to generate Fe-NO, Fe-CO and Fe-O<sub>2</sub> bonds respectively, and how the oxidation of heme iron by O<sub>2</sub> serves as a sensing mechanism that controls the activity of key proteins is complex and largely unclear. This is particularly important as many bacterial pathogens, including <i>Mtb</i> encounters three overlapping host gases (NO, CO and O<sub>2</sub>) during human infection. Future directions: Heme is an important prosthetic group that monitors the microbe's internal and external surroundings to alter signal transduction or enzymatic activation. Modern expression, metabolomic and biochemical technologies combined with <i>in vivo</i> pathogenesis studies should provide fresh insights into the mechanism of action of heme-based redox sensors.




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