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Rifampicin (Rif) is a first line drug used for tuberculosis treatment. However, the emergence of drug resistant strains has necessitated synthesis and testing of newer analogs of Rif.  Mycobacterium smegmatis  is often used as a surrogate for  M .  tuberculosis . However, the presence of an ADP ribosyltransferase (Arr) in  M .  smegmatis  inactivates Rif, rendering it impractical for screening of Rif analogs or other compounds when used in conjunction with them (Rif/Rif analogs). Rifampicin is also used in studying the role of various DNA repair enzymes by analyzing mutations in RpoB (a subunit of RNA polymerase) causing Rif resistance. These analyses use high concentrations of Rif when  M .  smegmatis  is used as model. Here, we have generated  M .  smegmatis  strains by deleting  arr  ( Δarr ). The  M .  smegmatis Δarr  strains show minimum inhibitory concentration (MIC) for Rif which is similar to that for  M .  tuberculosis . The MICs for isoniazid, pyrazinamide, ethambutol, ciprofloxacin and streptomycin were essentially unaltered for  M .  smegmatis Δarr . The growth profiles and mutation spectrum of  Δarr  and,  Δarr  combined with  ΔudgB  ( udgB  encodes a DNA repair enzyme that excises uracil) strains were similar to their counterparts wild-type for  arr . However, the mutation spectrum of  ΔfpgΔarr  strain differed somewhat from that of the  Δfpg  strain ( fpg  encodes a DNA repair enzyme that excises 8-oxo-G). Our studies suggest  M .  smegmatis Δarr  strain as an ideal model system in drug testing and mutation spectrum determination in DNA repair studies.

Use of Mycobacterium smegmatis Deficient in ADP-Ribosyltransferase as Surrogate for Mycobacterium tuberculosis in Drug Testing and Mutation Analysis