Disease relevance of msbB

• It was found that PgLPS(1435/1449) and PgLPS(1690) as well as E. coli msbB LPS activated a subset of those genes significantly transcribed in response to E. coli wild-type LPS [1].
• Antibacterial agents that target lipid A biosynthesis in gram-negative bacteria. Inhibition of diverse UDP-3-O-(r-3-hydroxymyristoyl)-n-acetylglucosamine deacetylases by substrate analogs containing zinc binding motifs [2].
• An Escherichia coli mutant lacking the cold shock-induced palmitoleoyltransferase of lipid A biosynthesis: absence of unsaturated acyl chains and antibiotic hypersensitivity at 12 degrees C [3].
• LpxXL is distantly related to the lauroyltransferase (LpxL) of E. coli lipid A biosynthesis, but highly significant LpxXL orthologues are present in Agrobacterium tumefaciens, Brucella melitensis, and all sequenced strains of Rhizobium, consistent with the occurrence of long secondary acyl chains in the lipid A molecules of these organisms [4].
• Modification of lipid A biosynthesis in Neisseria meningitidis lpxL mutants: influence on lipopolysaccharide structure, toxicity, and adjuvant activity [5].

High impact information on msbB

• A unique screen was used to identify mutations in Escherichia coli lipid A biosynthesis that result in a decreased ability to stimulate E-selectin expression by human endothelial cells [6].
• In our work, this is best illustrated by the analysis of phosphatidylglycerol-deficient mutants of E. coli, which provided the clue (i.e. lipid X) that permitted the elucidation of lipid A biosynthesis [7].
• UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group of UDP-GlcNAc [8].
• We have cloned and expressed the gene encoding UDP-N-acetylglucosamine 3-O-acyltransferase of C. trachomatis (CtlpxA), the first enzyme of lipid A biosynthesis [9].
• Determination of the proper attachment sites of these substituents is necessary for elucidating the enzymology of lipid A biosynthesis and for characterizing polymyxin-resistant mutants, in which l-Ara4N and pEtN substituents are greatly increased [10].

Chemical compound and disease context of msbB

• Two lipid A structural variants obtained from Porphyromonas gingivalis designated PgLPS(1435/1449) and PgLPS(1690) as well as LPS obtained from Escherichia coli wild type and an E. coli msbB mutant (missing myristic acid in the lipid A) were examined [1].
• However, the first seven enzymes of E. coli lipid A biosynthesis, leading from UDP-GlcNAc to the phosphorylated intermediate, 2-keto-3-deoxyoctulosonate (Kdo2)-lipid IVA, are present in R. leguminosarum [11].
• Over the past few years progress has been made in identifying the molecular mechanisms of host recognition of lipid A (a component of lipopolysaccharide), the identification of the genes required for Escherichia coli lipid A biosynthesis, and the role of lipid A acylation when viable bacteria are presented to host cells [12].
• Certain phosphatidylglycerol-deficient mutants of Escherichia coli accumulate two fatty acylated monosaccharides related to lipid A biosynthesis that have been identified as 2,3-diacylglucosamine 1-phosphate (lipid X) and triacylglucosamine 1-phosphate (lipid Y) (Raetz, C. R. H. (1984) Rev. Infect. Dis. 6, 463-472) [13].
• We propose that the addition of an R-3-hydroxymyristoyl residue to the 3 position of the GlcNAc moiety of UDP-GlcNAc is the first committed step in lipid A biosynthesis and that UDP-GlcNAc is situated at a biosynthetic branchpoint in E. coli leading either to lipid A or to peptidoglycan [14].

Biological context of msbB

• The unusual substrate specificity of these enzymes provides compelling evidence for their involvement in lipid A biosynthesis [15].
• The enzymes of lipid A biosynthesis, including LpxC, are encoded by single copy genes in all sequenced Gram-negative genomes [2].
• The envA permeability/cell division gene of Escherichia coli encodes the second enzyme of lipid A biosynthesis. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase [16].
• An msbB homologue carried in plasmid pO157 encodes an acyltransferase involved in lipid A biosynthesis in Escherichia coli O157:H7 [17].
• Here we show that at 37 degrees C LH530 contains a reduced amount of the OmpF porin and that it leaks periplasmic beta-lactamase at 37 degrees C and 42 degrees C. We further show that ORF195, when present at low copy number, restores the antibiotic resistance and lipid A biosynthesis of LH530 at 28 degrees C, but not at higher temperatures [18].

Associations of msbB with chemical compounds

• UDP-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA) catalyzes the reversible transfer of an R-3-hydroxyacyl chain from R-3-hydroxyacyl-acyl carrier protein to the glucosamine 3-OH of UDP-GlcNAc in the first step of lipid A biosynthesis [19].
• The ftsH1(Ts) mutation increased the amount of lipopolysaccharide at 42 degrees C. This was accompanied by a dramatic increase in the amount of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase [the IpxC (envA) gene product] involved in the committed step of lipid A biosynthesis [20].
• A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin [21].
• MsbB acylates (KDO)(2)-(lauroyl)-lipid IV-A with myristate during lipid A biosynthesis [22].
• The presence of a gene coding for an enzyme involved in lipid A biosynthesis between two genes coding for enzymes of the de novo purine biosynthesis pathway represents a unique arrangement of these genes [23].

References