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Gene Review

lpxM  -  myristoyl-acyl carrier protein (ACP)...

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK1856, JW1844, mlt, msbB, waaN
 
 
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Disease relevance of lpxM

 

High impact information on lpxM

  • We have demonstrated previously that tetra-acylated LPS derived from the oral bacterium, Porphyromonas gingivalis, and penta-acylated msbB LPS derived from a mutant strain of Escherichia coli can antagonize the ability of canonical hexa-acylated E. coli LPS to signal through the TLR4 signaling complex in human endothelial cells [4].
  • Inactivation of lpxM in both E. coli and S. typhimurium resulted in the loss of l-Ara4N addition, as well as, increased sensitivity to polymyxin [5].
  • However, extracts of msbB mutants do not efficiently acylate the product formed by HtrB, designated (Kdo)2-(lauroyl)-lipid IVA [6].
  • Extracts of strains harboring msbB+ bearing plasmids acylate (Kdo)2-(lauroyl)-lipid IVA very rapidly compared with wild type [6].
  • Experimental analyses showed that ecf1-4 formed an operon. ecf1, 2 and 3 encoded putative proteins associated with bacterial surface polysaccharide biosynthesis and invasion and ecf4 complemented a chromosomal deletion of lpxM encoding lipid A myristoyl transferase [7].
 

Chemical compound and disease context of lpxM

 

Biological context of lpxM

  • The msbB gene codes for a protein of 37,410 Da whose amino acid sequence is similar to that of HtrB and, like HtrB, the protein is very basic in nature [1].
  • Mutational analysis of msbB shows that the gene is not essential for E. coli growth; however, the htrB msbB double mutant exhibits a unique morphological phenotype at 30 degrees C not seen with either of the single mutants [1].
  • The mlt gene, which supposedly encodes Mlt, was cloned, and the complete nucleotide sequence was determined [9].
  • Escherichia coli msbB gene as a virulence factor and a therapeutic target [8].
  • These analyses also demonstrated an increase in the phosphorylation of lipid A and an increase in length of the oligosaccharide of a minor species of the msbB LOS [10].
 

Associations of lpxM with chemical compounds

  • Analysis of both msbB and htrB mutants shows that these bacteria are resistant to four times more deoxycholate than wild-type bacteria but not to other hydrophobic substances [1].
 

Analytical, diagnostic and therapeutic context of lpxM

  • Transmission and scanning electron microscopy studies indicated that the msbB mutants formed close associations with and were internalized by the uec at levels similar to those of the parent strain [10].

References

  1. Isolation and characterization of the Escherichia coli msbB gene, a multicopy suppressor of null mutations in the high-temperature requirement gene htrB. Karow, M., Georgopoulos, C. J. Bacteriol. (1992) [Pubmed]
  2. Modification of lipid A biosynthesis in Neisseria meningitidis lpxL mutants: influence on lipopolysaccharide structure, toxicity, and adjuvant activity. van der Ley, P., Steeghs, L., Hamstra, H.J., ten Hove, J., Zomer, B., van Alphen, L. Infect. Immun. (2001) [Pubmed]
  3. Transfer of mlt mutations into polyomavirus intronless genomes by intramolecular recombination in bacteria. Pinsonneault, C., Bouchard, L., Bastin, M. Gene (1988) [Pubmed]
  4. MD-2 mediates the ability of tetra-acylated and penta-acylated lipopolysaccharides to antagonize Escherichia coli lipopolysaccharide at the TLR4 signaling complex. Coats, S.R., Pham, T.T., Bainbridge, B.W., Reife, R.A., Darveau, R.P. J. Immunol. (2005) [Pubmed]
  5. Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A. Tran, A.X., Lester, M.E., Stead, C.M., Raetz, C.R., Maskell, D.J., McGrath, S.C., Cotter, R.J., Trent, M.S. J. Biol. Chem. (2005) [Pubmed]
  6. Function of the Escherichia coli msbB gene, a multicopy suppressor of htrB knockouts, in the acylation of lipid A. Acylation by MsbB follows laurate incorporation by HtrB. Clementz, T., Zhou, Z., Raetz, C.R. J. Biol. Chem. (1997) [Pubmed]
  7. Thermoregulation of the Escherichia coli O157:H7 pO157 ecf operon and lipid A myristoyl transferase activity involves intrinsically curved DNA. Yoon, J.W., Minnich, S.A., Ahn, J.S., Park, Y.H., Paszczynski, A., Hovde, C.J. Mol. Microbiol. (2004) [Pubmed]
  8. Escherichia coli msbB gene as a virulence factor and a therapeutic target. Somerville, J.E., Cassiano, L., Darveau, R.P. Infect. Immun. (1999) [Pubmed]
  9. Murein-metabolizing enzymes from Escherichia coli: existence of a second lytic transglycosylase. Engel, H., Smink, A.J., van Wijngaarden, L., Keck, W. J. Bacteriol. (1992) [Pubmed]
  10. Intracellular survival of Neisseria gonorrhoeae in male urethral epithelial cells: importance of a hexaacyl lipid A. Post, D.M., Phillips, N.J., Shao, J.Q., Entz, D.D., Gibson, B.W., Apicella, M.A. Infect. Immun. (2002) [Pubmed]
 
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