Table 1.

Endogenous NSAID targets in mycobacteria. These prospective targets and mechanisms are discussed in further detail throughout the review.

Putative targets for NSAIDs	Endogenous target mechanisms in mycobacteria	References
Translational Initiation	Ibuprofen and 2-arylpropanoic acids target traditional COX I & II in humans, additionally target RHO-GTPase. The homologue in M. tuberculosis is Translational initiation factor 2, InfB (Rv2839c) involved in protein synthesis initiation – identified as a possible target.	(Guzman et al., 2013)
Sliding Clamp/DNA Polymerase interaction	Inhibition of DNA polymerase III β subunit of Escherichia coli has been demonstrated using Carprofen.	(Yin et al., 2014)
Efflux pumps	Multiple drug efflux systems reported in M. tuberculosis and M. abscessus. Bedaquiline resistance has been attributed to the upregulation of MmpL5 and MmpS5 (Rv0676c and Rv0677c respectively). Mmp transporter proteins (MmpL5, MmpL6 and MmpS5) have been identified as a possible target as they are upregulated by Carprofen and Ibuprofen in M. smegmatis.	(Maitra et al., 2020, Hartkoorn et al., 2014)
Biofilm formation	M. tuberculosis can form biofilms, demonstrated by murine modelling. Complete inhibition of M. smegmatis biofilm formation has been determined at 250 mg/L (1 × MIC) of Carprofen.	(Maitra et al., 2020)
Membrane potential	Membrane potential of M. tuberculosis was disrupted by Carprofen, but not to the same extent as other known disruptors such as carbonyl cyanide m-chlorophenylhydrazone (CCCP), also a known efflux inhibitor disrupting the proton motive force (PMF).	(Maitra et al., 2020)