Approximately one third of the world population is infected with Mycobacterium 
tuberculosis, the causative agent of tuberculosis. A better understanding of the 
pathogen biology is crucial to develop new tools/strategies to tackle its spread 
and treatment. In the host macrophages, the pathogen is exposed to reactive 
oxygen species, known to damage dGTP and GTP to 8-oxo-dGTP and 8-oxo-GTP, 
respectively. Incorporation of the damaged nucleotides in nucleic acids is 
detrimental to organisms. MutT proteins, belonging to a class of Nudix 
hydrolases, hydrolyze 8-oxo-G nucleoside triphosphates/diphosphates to the 
corresponding nucleoside monophosphates and sanitize the nucleotide pool. 
Mycobacteria possess several MutT proteins. However, a functional homolog of 
Escherichia coli MutT has not been identified. Here, we characterized MtuMutT1 
and Rv1700 proteins of M. tuberculosis. Unlike other MutT proteins, MtuMutT1 
converts 8-oxo-dGTP to 8-oxo-dGDP, and 8-oxo-GTP to 8-oxo-GDP. Rv1700 then 
converts them to the corresponding nucleoside monophosphates. This observation 
suggests the presence of a two-stage mechanism of 8-oxo-dGTP/8-oxo-GTP 
detoxification in mycobacteria. MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP with 
a Km of ∼50 μM and Vmax of ∼0.9 pmol/min per ng of protein, and Rv1700 converts 
8-oxo-dGDP to 8-oxo-dGMP with a Km of ∼9.5 μM and Vmax of ∼0.04 pmol/min per ng 
of protein. Together, MtuMutT1 and Rv1700 offer maximal rescue to E. coli for 
its MutT deficiency by decreasing A to C mutations (a hallmark of MutT 
deficiency). We suggest that the concerted action of MtuMutT1 and Rv1700 plays a 
crucial role in survival of bacteria against oxidative stress.