Disease relevance of SF-1902A1

• Cleavage of the pilin leader peptide is independent of known signal peptidases as demonstrated by pilin-processing profiles in Escherichia coli strains conditionally defective for production of leader peptidase or grown in the presence of the antibiotic globomycin [1].
• The lipoprotein nature of FatB is supported by the fact that treatment of Vibrio anguillarum cells with globomycin, an inhibitor of the lipoprotein signal peptidase, results in the accumulation of a 38 kDa proFatB precursor protein [2].
• In the current study, we showed that the product of the cloned gene could be labelled with palmitic acid, that it was subject to globomycin-sensitive processing, and that it was immunologically cross-reactive with azurin from Pseudomonas aeruginosa [3].
• The use of the antibiotic globomycin in a minicell expression system and radioimmunoprecipitation analysis of Hib proteins intrinsically radiolabelled with [3H]-palmitate indicated that the 51K haemin-binding protein is a lipoprotein [4].
• When the mycoplasma cell concentration was varied from 10(4) to 10(8) CFU/ml, the MICs of enrofloxacin and globomycin increased while those of the three other molecules remained essentially constant [5].

High impact information on SF-1902A1

• Under the same conditions, globomycin does not prevent the attachment of palmitate or glycerol to the E. coli prolipoprotein but inhibits processing of the modified precursor to the mature lipoprotein [6].
• The peptide antibiotic globomycin, which prevents processing of the E. coli prolipoprotein, severely inhibited the attachment of [3H]palmitate or [3H]glycerol to the 749/C enzyme (either in B. licheniformis 749/C or in E. coli), blocked the accumulation of penicillinase in the plasma membrane, and enhanced the formation of exoenzyme [6].
• These results are in contrast with the lack of effect of globomycin on the RTEM-beta-lactamase of E. coli which has no detectable hydrophobic membrane form and was not labeled with palmitate or glycerol [6].
• Overexpression, membrane fractionation, and metabolic labeling with [3H]palmitate demonstrated that Blc is indeed a globomycin-sensitive outer membrane lipoprotein [7].
• Experiments with globomycin presented here also suggest that the primary precursor of EGL (ppEGL) has a 45-residue leader sequence but that only the first 19 residues of the leader sequence are removed by signal peptidase II during initial export across the inner membrane [8].

Chemical compound and disease context of SF-1902A1

• This enzyme is globomycin sensitive and has been purified 35,000-fold from the membranes of Escherichia coli by extraction at pH 4.0 with 2% Triton X-100 and heating, followed by conventional column chromatography at room temperature [9].
• Inhibition by globomycin indicated a lipid modification at the N-terminal cysteine in E. coli [10].
• In the present work, the in vitro susceptibility of M. pulmonis, a murine pathogen, to enrofloxacin and four AMPs (alamethicin, globomycin, gramicidin S, and surfactin) was investigated, with special reference to synergistic associations and the effect of the mycoplasma cell concentration [5].
• A globomycin-resistant mutant of Escherichia coli was found to produce a precursor of the major outer membrane lipoprotein (prolipoprotein), in which the glycine residue at position 14 within the signal peptide was replaced by an aspartic acid residue [11].
• When a lipoprotein-deficient (lpp) mutant of Escherichia coli was transformed with pBR322 carrying the S. marcescens lpp gene, cells became nonleaky for ribonuclease, resistant to ethylenediaminetetraacetic acid, and sensitive to globomycin [12].

Biological context of SF-1902A1

• The plasmid pMT521, a subclone of pLC3-13 in pBR322, conferred on its host cells approximately 20 times overproduction of prolipoprotein signal peptidase and an extremely high level of resistance against globomycin [13].
• The incorporation of exogenous [1-14C]palmitate into phosphatidylethanolamine in fadD mutants was inhibited by chloramphenicol and was depressed by preventing the acylation of the amino terminus of the lipoproteins with the antibiotic globomycin [14].
• Three revertants were chosen in the present study which included the analysis of kinetics of lipoprotein maturation and the determination of globomycin sensitivity [15].
• Lipoprotein fatty acids derived from the 1-position of phosphatidylethanolamine were resistant to hydroxylamine hydrolysis, and globomycin reduced the incorporation of exogenous [1-14C]palmitate into lipoproteins by 80% suggesting that this fatty acid is primarily attached to the amino terminus of the lipoprotein [14].
• As predicted by the DNA sequence, the recombinant 15 kiloDalton immunogen labelled selectively with [3H]-palmitate, and globomycin inhibited processing of the precursor to the mature polypeptide [16].

Anatomical context of SF-1902A1

• Existence of the bound form of prolipoprotein in Escherichia coli B cells treated with globomycin [17].
• Formation of spheroplasts was observed when Escherichia coli was grown in the presence of globomycin, indicating inhibition of the bacterial cell wall synthesis as its mode of action [18].
• Treatment with the signal peptidase inhibitor globomycin inhibits ATX secretion by adipocytes [19].

Associations of SF-1902A1 with other chemical compounds

• Globomycin treatment, Triton X-114 separation and mass spectrometry analyses clarified a property of the Rv0679c protein as a lipoprotein [20].
• However, globomycin depolarized the plasma membrane only weakly, whilst polymyxin B, in order to be active, required prior hyperpolarization of the membrane [21].
• Furthermore, the use of the potential-sensitive fluorescent dye 3,3'-dipropyl-2,2'-thiadicarbocyanine iodide (diS-C3-[5]) revealed that, in contrast to valinomycin and mellitin, globomycin up to 30 microM has no effect on the electrical transmembrane potential of S. melliferum [22].

Gene context of SF-1902A1

• A slightly larger precursor molecule is detected when minicells expressing nlpB are treated with globomycin, a specific inhibitor of lipoprotein signal peptidase [23].
• Isolation and characterization of a new globomycin-resistant dnaE mutant of Escherichia coli [24].
• The pilN product was shown to be a lipoprotein by an experiment using globomycin [25].
• VirB7 was shown to be processed as a lipoprotein by (i) in vivo labeling of native VirB7 and a VirB7::PhoA fusion with [3H]palmitic acid and (ii) inhibition of VirB7 processing by globomycin, a known inhibitor of signal peptidase II [26].
• Growth of E. coli cells expressing the cloned H. pylori lpp20 gene in the presence of [3H]palmitic acid resulted in radiolabelled Lpp20 while treatment of the E. coli cells with globomycin caused accumulation of unprocessed Lpp20, consistent with Lpp20 being a lipoprotein [27].

Analytical, diagnostic and therapeutic context of SF-1902A1

• Immunoblotting analysis using the antibody against the 45-kDa protein revealed a 48-kDa precursor of the protein, which accumulated in the cyanobacterial cells treated with globomycin, an antibiotic that specifically inhibits cleavage of the signal peptide of lipoprotein precursors [28].
• After treatment with globomycin, a significant amount of this modified precursor form accumulated and was degraded with time into smaller acylated proteins, but without release of the signal peptide [29].
• SDS-PAGE analysis of cell proteins followed by immunolabeling ("Western blotting") and by crossed immunoelectrophoresis demonstrated that the cleavage of the prespiralin leader peptide was prevented by globomycin [22].

References