The ada operon of Mycobacterium tuberculosis encodes two DNA methyltransferases for inducible repair of DNA alkylation damage

Biochemical and Structural Studies of the Mycobacterium tuberculosis O 6 -Methylguanine Methyltransferase and Mutated Variants

“…Paralleling observations of other bacteria (13), the mycobacterial OGT-encoding sequence (adaB; Rv1316c) is part of an adaptive response operon, which was recently functionally characterized (14). Gene inactivation experiments demonstrated that adaB (here referred to as OGT, in analogy to orthologs in other species) is not essential for infectivity and survival either in vitro or in the mouse model of M. tuberculosis infection (15,16).…”

“…Interestingly, two nonsynonymous single-nucleotide polymorphisms (nsSNPs) have been identified in the OGT genes of both M. tuberculosis Beijing strains and multidrug-resistant isolates (19)(20)(21), leading several authors to postulate that corresponding mutated OGTs may contribute to the success of these strains in terms of worldwide distribution; indeed, it has been suggested that a defective OGT might result in an increased mutation frequency and, thus, in a better capability of the bacterium to rapidly adapt to the host (14,19).…”

“…However, several observations support the importance of OGT activity in protecting the mycobacterial GC-rich DNA from the promutagenic potential of guanine O 6 -methylation. First, the OGT gene expression profile changes during infection and in response to alkylating compounds (14,17,18), signaling a requirement for fine-tuned OGT modulation under stressful conditions; moreover, the heterologous expression of M. tuberculosis OGT (MtOGT) in the Escherichia coli KT233 ada-ogt-defective strain suppresses its MNNG (N-methyl-N=-nitro-N-nitrosoguanidine) sensitivity (14) and rescues the hypermutator phenotype.…”

Beijing Sublineages of Mycobacterium tuberculosis Differ in Pathogenicity in the Guinea Pig

“…Rv1317c (alkA) is part of the AdaA-AlkA adaptive response in M. tuberculosis, and multiple mutations have been found in strains from lineage 4 (Euro-American), lineage 2 (the same mutation has been found previously in the W-Beijing 210 strain, which belongs to the RD142 sublineage), and in Mycobacterium bovis (29). It has been suggested that a defective adaptive response by these genes will confer a selective advantage to M. tuberculosis (54).…”

DNA Repair and Genome Maintenance in Bacillus subtilis

“…For a complete and comprehensive review of the E. coli Ada response, we direct readers to previously published reviews (128,376,430). The Ada response occurs in many Gramnegative bacteria as well as some Gram-positive bacteria, including but not limited to B. subtilis, Bacillus thuringiensis, M. tuberculosis, and Micrococcus luteus (340,341,463). The Ada response is a transcriptional response that was originally referred to as "the adaptive response to alkylation damage," because pretreatment of E. coli cells with small doses of alkylating agents guarded cells against the effects of higher doses (128,167,168,359,376,430).…”