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Gene Review

rrs  -  16S ribosomal RNA

Mycobacterium tuberculosis H37Rv

 
 
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Disease relevance of rrs

  • An A1400G mutation of the rrs gene was identified in Mycobacterium tuberculosis (MTB) strain ATCC 35827 and in 13 MTB clinical isolates resistant to amikacin-kanamycin (MICs, >128 microg/ml) [1].
 

High impact information on rrs

  • Streptomycin resistance in about one-half of M. tuberculosis isolates is associated with missense mutations in the rpsL gene coding for ribosomal protein S12 or nucleotide substitutions in the 16S rRNA gene (rrs) [2].
  • The rrs genes of all mutants were sequenced, and the tlyA genes were sequenced for mutants selected on capreomycin, viomycin, or both; MICs of all four drugs were determined [3].
  • Mutations in the 16S rRNA gene (rrs) have been associated with resistance to each of the drugs; however, reports of cross-resistance to the drugs have been variable [3].
  • We investigated the role of rrs mutations in capreomycin resistance and examined the molecular basis of cross-resistance to the four drugs in M. tuberculosis laboratory-generated mutants and clinical isolates [3].
  • Molecular characterization of a streptomycin-dependent mutant of Mycobacterium tuberculosis revealed the presence of a novel mutation in the rrs gene encoding 16S rRNA [4].
 

Chemical compound and disease context of rrs

 

Biological context of rrs

  • Although such resistance is often mediated by mutations within rrs, a 16S rRNA gene or rpsL, which encodes the ribosomal protein S12, these mutations are found in a limited proportion of clinically isolated streptomycin-resistant M. tuberculosis strains [6].
  • Of the 98 SM-resistant isolates, 78 (79.6%) had missense mutations in codon 43 or 88 of rpsL resulting in a Lys to Arg substitution, 6 (6.1%) had mutations of the rrs gene at positions 513 A to C or T or 516 C to T, and 14 (14.3%) had the wild-type sequence [7].
  • To investigate the extent to which mutations in a specific region of the rrs gene and the kanamycin-resistant phenotype in clinically isolated M. tuberculosis strains were correlated, 43 kanamycin-resistant strains (MICs, > or =200 microg/ml), 71 kanamycin-susceptible strains, and 4 type strains were examined [5].
  • The 300-bp DNA fragments carrying the rrs gene and the intervening sequence between the rrs gene and 23S rRNA (rrl) gene fragments were amplified by PCR and were subjected to PCR-based direct sequencing [5].
 

Associations of rrs with chemical compounds

  • All of the M. smegmatis strains with high-level kanamycin resistance had a nucleotide substitution from A to G at position 1389 of the 16S rRNA gene (rrs) [8].

References

  1. Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis. Alangaden, G.J., Kreiswirth, B.N., Aouad, A., Khetarpal, M., Igno, F.R., Moghazeh, S.L., Manavathu, E.K., Lerner, S.A. Antimicrob. Agents Chemother. (1998) [Pubmed]
  2. Antimicrobial agent resistance in mycobacteria: molecular genetic insights. Musser, J.M. Clin. Microbiol. Rev. (1995) [Pubmed]
  3. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Maus, C.E., Plikaytis, B.B., Shinnick, T.M. Antimicrob. Agents Chemother. (2005) [Pubmed]
  4. Novel mutation in 16S rRNA associated with streptomycin dependence in Mycobacterium tuberculosis. Honoré, N., Marchal, G., Cole, S.T. Antimicrob. Agents Chemother. (1995) [Pubmed]
  5. Detection of kanamycin-resistant Mycobacterium tuberculosis by identifying mutations in the 16S rRNA gene. Suzuki, Y., Katsukawa, C., Tamaru, A., Abe, C., Makino, M., Mizuguchi, Y., Taniguchi, H. J. Clin. Microbiol. (1998) [Pubmed]
  6. Loss of a conserved 7-methylguanosine modification in 16S rRNA confers low-level streptomycin resistance in bacteria. Okamoto, S., Tamaru, A., Nakajima, C., Nishimura, K., Tanaka, Y., Tokuyama, S., Suzuki, Y., Ochi, K. Mol. Microbiol. (2007) [Pubmed]
  7. Detection of streptomycin resistance in Mycobacterium tuberculosis clinical isolates using four molecular methods in China. Wu, X.Q., Lu, Y., Zhang, J.X., Liang, J.Q., Zhang, G.Y., Li, H.M., Lü, C.H., Ding, B.C. Yi Chuan Xue Bao (2006) [Pubmed]
  8. Molecular analysis of kanamycin and viomycin resistance in Mycobacterium smegmatis by use of the conjugation system. Taniguchi, H., Chang, B., Abe, C., Nikaido, Y., Mizuguchi, Y., Yoshida, S.I. J. Bacteriol. (1997) [Pubmed]
 
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