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Gene Review

murM  -  serine/alanine adding enzyme

Streptococcus pneumoniae R6

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Disease relevance of murM


High impact information on murM

  • Several different alleles of murM cloned in plasmid pLS578 and introduced into a murM deletion mutant of the penicillin-resistant strain Pen6 were able to reconstitute each one of the three mutant phenotypes: the highly branched cell wall structure, original high level of penicillin resistance, and normal sensitivity to lysis [2].
  • We now show that the genome of S. pneumoniae contains an operon composed of two genes (murM and murN) that encode enzymes involved with the biosynthesis of branched structured cell wall muropeptides [3].
  • This suggests that the muropeptide composition of the pneumococcal cell walls is determined by the particular murM allele carried by the cells [4].
  • Different murM alleles from several penicillin-resistant S. pneumoniae strains, each with a characteristic branched peptide pattern, were cloned into pLS578, a pneumococcal plasmid capable of replicating in S. pneumoniae, and transformed into the penicillin-susceptible laboratory strain R36A [4].
  • The adr mutant has retained unchanged (low affinity) PBPs, unaltered murM gene and unchanged cell wall stem peptide composition, but the mutant became hypersensitive to exogenous lysozyme and complementation experiments showed that both phenotypes - reduced resistance and lysozyme sensitivity - were linked to the defective adr gene [5].

Chemical compound and disease context of murM


Associations of murM with chemical compounds

  • Further transformation with altered murM DNA was required for full expression of donor penicillin and cefotaxime resistance [7].
  • In addition, the presence of specific mutations in PBP2B seems to play a key role in the presence of different murM alleles in these amoxicillin-resistant pneumococcal strains [6].

Other interactions of murM

  • Different protein variants of MurM (MA, MB5, MB6, MB9 and MB10), PBP1A (A-C), PBP2B (A-D) and PBP2X (A-C) were recognized, including two murM alleles not previously described [8].

Analytical, diagnostic and therapeutic context of murM


  1. Distribution of the mosaic structured murM genes among natural populations of Streptococcus pneumoniae. Filipe, S.R., Severina, E., Tomasz, A. J. Bacteriol. (2000) [Pubmed]
  2. The murMN operon: a functional link between antibiotic resistance and antibiotic tolerance in Streptococcuspneumoniae. Filipe, S.R., Severina, E., Tomasz, A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Inhibition of the expression of penicillin resistance in Streptococcus pneumoniae by inactivation of cell wall muropeptide branching genes. Filipe, S.R., Tomasz, A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Functional analysis of Streptococcus pneumoniae MurM reveals the region responsible for its specificity in the synthesis of branched cell wall peptides. Filipe, S.R., Severina, E., Tomasz, A. J. Biol. Chem. (2001) [Pubmed]
  5. Attenuation of penicillin resistance in a peptidoglycan O-acetyl transferase mutant of Streptococcus pneumoniae. Crisóstomo, M.I., Vollmer, W., Kharat, A.S., Inhülsen, S., Gehre, F., Buckenmaier, S., Tomasz, A. Mol. Microbiol. (2006) [Pubmed]
  6. Alterations of the penicillin-binding proteins and murM alleles of clinical Streptococcus pneumoniae isolates with high-level resistance to amoxicillin in Spain. Cafini, F., del Campo, R., Alou, L., Sevillano, D., Morosini, M.I., Baquero, F., Prieto, J. J. Antimicrob. Chemother. (2006) [Pubmed]
  7. Alterations in MurM, a cell wall muropeptide branching enzyme, increase high-level penicillin and cephalosporin resistance in Streptococcus pneumoniae. Smith, A.M., Klugman, K.P. Antimicrob. Agents Chemother. (2001) [Pubmed]
  8. Combinations of PBPs and MurM protein variants in early and contemporary high-level penicillin-resistant Streptococcus pneumoniae isolates in Spain. Del Campo, R., Cafini, F., Morosini, M.I., Fenoll, A., Liñares, J., Alou, L., Sevillano, D., Cantón, R., Prieto, J., Baquero, F. J. Antimicrob. Chemother. (2006) [Pubmed]
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