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Literature summary for 2.1.1.226 extracted from

  • Freihofer, P.; Akbergenov, R.; Teo, Y.; Juskeviciene, R.; Andersson, D.; Boettger, E.
    Nonmutational compensation of the fitness cost of antibiotic resistance in mycobacteria by overexpression of tlyA rRNA methylase (2016), RNA, 22, 1836-1843 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
additional information generation of a tlyA deletion mutant Mycobacterium tuberculosis

Localization

Localization Comment Organism GeneOntology No. Textmining
ribosome
-
Mycobacterium tuberculosis 5840
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-adenosyl-L-methionine + cytidine1920 in 23S rRNA Mycobacterium tuberculosis
-
S-adenosyl-L-homocysteine + 2'-O-methylcytidine1920 in 23S rRNA
-
?
S-adenosyl-L-methionine + cytidine1920 in 23S rRNA Mycobacterium tuberculosis H37Rv
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S-adenosyl-L-homocysteine + 2'-O-methylcytidine1920 in 23S rRNA
-
?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WJ63
-
-
Mycobacterium tuberculosis H37Rv P9WJ63
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the bifunctional enzyme exhibits the activities of EC 2.1.1.226 and EC 2.1.1.227 Mycobacterium tuberculosis ?
-
-
additional information the bifunctional enzyme exhibits the activities of EC 2.1.1.226 and EC 2.1.1.227 Mycobacterium tuberculosis H37Rv ?
-
-
S-adenosyl-L-methionine + cytidine1920 in 23S rRNA
-
Mycobacterium tuberculosis S-adenosyl-L-homocysteine + 2'-O-methylcytidine1920 in 23S rRNA
-
?
S-adenosyl-L-methionine + cytidine1920 in 23S rRNA
-
Mycobacterium tuberculosis H37Rv S-adenosyl-L-homocysteine + 2'-O-methylcytidine1920 in 23S rRNA
-
?

Synonyms

Synonyms Comment Organism
More see also EC 2.1.1.227 Mycobacterium tuberculosis
rRNA methylase
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Mycobacterium tuberculosis
rRNA methylase TlyA
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Mycobacterium tuberculosis
TlyA
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Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
S-adenosyl-L-methionine
-
Mycobacterium tuberculosis

Expression

Organism Comment Expression
Mycobacterium tuberculosis in response to capreomycin, cells downregulate TlyA-mediated methylation of 16S and 23S (cf. EC 2.1.1.226) rRNA resulting in decreased drug susceptibility. Incubation with capreomycin during bacterial growth results in a reduced post-transcriptional modification of rRNA at TlyA-dependent sites (1409 in 16S and 1920 in 23S) down
Mycobacterium tuberculosis the common resistance mutation A1408G is accompanied by a physiological change that involves increased expression of the tlyA gene up

General Information

General Information Comment Organism
malfunction loss-of-function mutations in rRNA methylase TlyA or point mutations in 16S rRNA, in particular the A1408G mutation. Both of these alterations result in resistance by reducing drug binding to the ribosome. Alterations of tlyA gene expression affect both antibiotic drug susceptibility and fitness cost of drug resistance. In particular, the common resistance mutation A1408G is accompanied by a physiological change that involves increased expression of the tlyA gene. This gene encodes an enzyme that methylates neighboring 16S rRNA position C1409, and as a result of increased TlyA expression the fitness cost of the A1408G mutation is significantly reduced Mycobacterium tuberculosis
metabolism antibiotic resistance mechanisms frequently confer a fitness cost, and these costs can be genetically ameliorated by intra- or extragenic second-site mutations, often without loss of resistance. Another mechanism by which the fitness cost of antibiotic resistance can be reduced is via a regulatory response where the deleterious effect of the resistance mechanism is lowered by a physiological alteration that buffers the mutational effect. In mycobacteria, resistance to the clinically used tuberactinomycin antibiotic capreomycin involves loss-of-function mutations in rRNA methylase TlyA or point mutations in 16S rRNA, in particular the A1408G mutation. Both of these alterations result in resistance by reducing drug binding to the ribosome. In mycobacteria, this nonmutational mechanism (i.e. gene regulatory) can restore fitness to genetically resistant bacteria. Incubation with capreomycin during bacterial growth resulted in a reduced post-transcriptional modification of rRNA at TlyA-dependent sites (1409 in 16S and 1920 in 23S), cf. EC 2.1.1.226 Mycobacterium tuberculosis
physiological function TlyA methylase modifies the rRNA position 1409, reducing the cost of the A1408G mutation while concomitantly also reducing the antibiotic resistance level, e.g. against capreomycin and viomycin. In response to capreomycin, cells downregulate TlyA-mediated methylation of 16S and 23S rRNA resulting in decreased drug susceptibility. Increased TlyA expression reduces resistance in the A1408G mutant and concomitantly increases fitness Mycobacterium tuberculosis