Mechanism of action of globomycin.

Inukai, Masatoshi; Takeuchi, Michiko; Shimizu, Keiko; Arai, Mamoru

doi:10.7164/antibiotics.31.1203

Cited by 215 publications

(150 citation statements)

References 7 publications

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“…4). The presence of a signal peptidase II consensus site in PCPYe predicted that the processing of the precursor would not occur in the presence of globomycin, a specific inhibitor of signal peptidase II (18). Indeed, processing of the 14-kDa precursor was inhibited by the antibiotic (Fig.…”

Section: Methodsmentioning

confidence: 99%

A lipoprotein of Yersinia enterocolitica facilitates ferrioxamine uptake in Escherichia coli

Bäumler

Hantke

1992

J Bacteriol

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A cloned fragment of Yersinia enterocolitica DNA complemented the defect in ferrioxamine B uptake of an Escherichia coli fluE mutant lacking the outer membrane high-affinity transport protein FhuE. Subcloning revealed that a 13.7-kDa outer membrane protein was required for complementation. The amino acid sequence deduced from the nucleotide sequence showed extensive homology to PCPHI, an outer membrane lipoprotein of Haemophilus influenzae. We therefore termed this protein PCPye. Plasmid-encoded pcpY mediated a low-affinity uptake of ferrioxamine B which may be caused by changes in the permeability of the outer membrane due to an overexpression of this outer membrane protein. A transposon insertion mutant in the plasmid-encoded pcpY gene was transferred into the chromosome of Y. enterocolitica. The resulting mutation had no effect on the high-affinity uptake of ferrioxamine B in Yersinia cells. Using the antibiotic ferrimycin we were able to isolate a Y. enterocolitica mutant lacking the high-affinity outer membrane receptor for ferrioxamine uptake, termed FoxA.Yersinia pestis, Yersinia enterocolitica, and Yersinia pseudotuberculosis are pathogenic in humans, causing diseases ranging from enteritis to black death by invasion of host tissues. Of these species, Y. enterocolitica is now the one most frequently isolated from human and animal infections.Ferrioxamine B can promote growth of Y. enterocolitica in vitro (6, 24) and in vivo (26) by acting as a source of iron for the organism. In strains which do not produce a siderophore (15), virulence in mice can be enhanced by addition of either iron dextran or the iron chelator desferrioxamine B (26). Desferrioxamine B is sold under the name Desferal as a licensed therapeutic substance for use in patients suffering from iron overload. Hence, it seems that treatment with desferrioxamine B increases the susceptibility of patients to yersiniosis (21) by serving as a siderophore, which helps Y. enterocolitica to obtain iron under the conditions of iron starvation in the host (7). It should be noted, though, that this effect could also be a consequence of the immunosuppressive activity of ferrioxamine B (2, 8).Siderophore uptake has been studied in detail in Escherichia coli. Each siderophore is transported across the outer membrane via a specific receptor protein. This process has been shown to be energy dependent and requires the action of the TonB protein, which is thought to couple the membrane potential of the cytoplasmic membrane with the outer membrane proteins by direct contact. Transport through the cytoplasmic membrane is mediated by a periplasmic binding protein-dependent transport system. This type of transport seems to be realized in various gram-negative genera for the uptake of vitamin B12 and siderophores (for a recent review, see reference 5). The coprogen outer membrane receptor protein FhuE (30) of E. coli mediates uptake of ferrioxamine B to a small extent.In this study we describe an attempt to clone the ferrioxamine B uptake system of Y. enterocolitic...

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Section: Methodsmentioning

confidence: 99%

A lipoprotein of Yersinia enterocolitica facilitates ferrioxamine uptake in Escherichia coli

Bäumler

Hantke

1992

J Bacteriol

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“…One exception within this criterion is the Cu,Zn superoxide dismutase Lpp of Mycobacterium tuberculosis where non-denaturing electrophoresis indicated that the native membrane-associated enzyme activity is electrophoretically identical to that which has been radiolabelled with palmitate upon expression in E. coli (D'Orazio et al, 2001). (2) Inhibition of Lpp signal peptide processing by treatment with the antibiotic globomycin, which specifically inhibits Lsp (Inukai et al, 1978). (3) Chemical characterization of the purified protein.…”

Section: Methodsmentioning

confidence: 99%

Pattern searches for the identification of putative lipoprotein genes in Gram-positive bacterial genomes

2002

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INTRODUCTIONThe bacterial cell envelope is of major significance as the focal point for interaction between the bacterium and its environment, notably the host in the case of bacterial pathogens. Bacterial cell envelope proteins thus carry out numerous important functions including roles in adhesion, nutrient acquisition and a variety of interactions with host defences. In Gram-positive bacteria the matrix of peptidoglycan and other wall polymers surrounding the cell is not an efficient barrier to the passage of small macromolecules, due both to its inherent structural permeability and to its turnover during normal cell growth. Indeed, peptidoglycan may be sufficiently permeable as to allow the passage of globular proteins of up to "50 kDa in size (Demchick & Koch, 1996 ;Dijkstra & Keck, 1996). Consequently, in the absence of a retentive outer membrane, Grampositive bacteria have evolved distinct mechanisms for retaining proteins within their cell envelopes, including covalent linkage to the peptidoglycan and non-covalent binding to teichoic acids and other cell envelope polymers (Navarre & Schneewind, 1999 ;Cossart & Jonquieres, 2000 ;Janulczyk & Rasmussen, 2001). Also significant among these mechanisms is membraneanchoring of bacterial lipoproteins (Lpps) by covalent N-terminal lipidation (Braun & Wu, 1994 ; Sutcliffe & Russell, 1995). Lpps in Gram-positive bacteria perform important roles as substrate-binding proteins (SBPs) in ABC transporter systems ; in antibiotic resistance ; in cell signalling ; in protein export and folding ; in sporulation and germination ; in conjugation and various other functions (Sutcliffe & Russell, 1995 valent to those carried out by periplasmic proteins of Gram-negative bacteria.The archetypal bacterial Lpp is the murein lipoprotein of Escherichia coli characterized by Braun and coworkers (reviewed in Braun & Wu, 1994). Structural studies revealed that a diacylglycerol moiety is thioether linked to an N-terminal cysteine of this Lpp and that this lipid group serves to orientate the protein by anchoring it to the inner leaflet of the outer membrane. Chemically identical lipid modifications have since been proposed, primarily on the basis of protein sequence analysis (see below), for a great many proteins in both Gram-positive and Gram-negative bacteria, although relatively few have received extensive biochemical characterization.Biosynthesis of bacterial lipoprotein of the ' Braun ' type proceeds via a well conserved pathway that is apparently unique to prokaryotes (Fig. 1). Following signal-peptidedirected export of the prolipoprotein (proLpp), the enzyme prolipoprotein diacylglycerol transferase (Lgt) uses phospholipid substrates and catalyses the addition of a diacylglycerol lipid unit onto the thiol of a crucial conserved cysteine which is located within a ' lipobox ' motif at the cleavage region of the proLpp signal peptide (Sankaran et al., 1995 ; Qi et al., 1995). Subsequently, the signal peptide is removed by a specific lipoprotein signal peptidase II (Lsp) enzyme which ...

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“…Antibodies raised against purified CBP cross-reacted with one '"C-labelled protein of 45 kDa, which was preferentially found within the membrane fraction. Globomycin is known to inhibit the processing of lipoproteins (Inukai et al, 1978). If globomycin (75 pg/ml) was applied to growing cultures, together with [l-'4C]palmitic acid, the molecular mass of several '"C-labelled proteins increased, and two of them cross-reacted with the antibodies.…”

Section: Metabolic Labelling Of Lipoproteins With [L-'4c]palmitic Acidmentioning

confidence: 99%

A Lipid‐Anchored Binding Protein is a Component of an ATP‐Dependent Cellobiose/Cellotriose‐Transport System from the Cellulose Degrader Streptomyces reticuli

Schlösser

Schrempf

1996

European Journal of Biochemistry

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During cultivation in the presence of cellobiose or crystalline cellulose, Streptomyces reticuli expresses an inducible uptake system that transports cellobiose (K,,,, 4 pM), cellotriose and, to a lesser degree, cellotetraose and cellopentaose. Cellobiose uptake is dependent on ATP and inhibited by Nethylmaleimide. A binding protein was identified in its palmitylated form in the cytoplasmic membrane of mycelia. It could be extracted with the detergent Triton X-100 and purified by two subsequent anionexchange chromatographies. It showed highest affinity (&, 1 .5 pM) for cellobiose and cellotriose. The data suggest that cellobiose/cellotriose uptake is mediated by a membrane-anchored lipoprotein as a component of an ATP-binding-cassette-transporter system. Keywords : Streptomyces reticuli ; cellobiose/cellotriose transport ; vesicle ; lipoprotein ; uptake of glucose.Although Streptomycetes may utilize a number of sugars for growth, knowledge about the pathways of carbohydrate metabolism and their regulation is still limited (Romano, 1986). Transport studies indicated the presence of glucose-uptake systems in Streptomyces clavuligerus (Garcia-Dominguez et al., 1989), and an inducible cellobiose-transport system in Streptomyces grunaticolor (Jiresovg et al., 1987). The mechanisms for sugar uptake in Streptomycetes remain to be elucidated by means of biochemical and molecular-biological techniques. Recently a few Streptomyces sp. were shown to contain proteins that may belong to a fructose-specific phosphotransferase (PTS)system. However, a phosphoenolpyruvate-dependent transport of any sugar has not been demonstrated (Titgemeyer et al., 1995 ;Novotna and Hostalek, 1985). The cellobiose-uptake operons from Escherichiu coli (Kricker and Hall, 1987) and Bucillus stearothermophilus (Lai and Ingram, 1993) encode cellobiose-specific components of a PTS system.Within other bacteria, different types of sugar-transport systems have been identified. In addition to various PTS systems, binding-protein-dependent transport systems are encountered, which belong to the superfamily of ATP-binding-cassette transporters or traffic ATPases Higgins, 1992). These systems typically consist of five proteins (Ames, 1986): a soluble or membrane-associated binding protein ; two identical or similar integral membrane proteins; and two identical or similar ATP-binding proteins. The latter are oriented towards the cytoplasm, and couple the hydrolysis of ATP to the transport process . In gram-negative bacteria, binding proteins are located in the periplasmic space, whereas in the few studied gram-positive bacteria, they were found linked to the surface of the cytoplasmic membrane by a lipid anchor (Alloing et al., 1994;Sutcliffe and Russell, 1995 as sugars, amino acids, oligopeptides and vitamins. In addition to these binding-protein-dependent systems, bacteria contain secondary transport systems that couple the uptake of solutes to the proton-motive force (Krulwich, 1990).Previously, we identified a StreptomyceJ reticuli cellulace (Avicelase,...

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Mechanism of action of globomycin.

Cited by 215 publications

References 7 publications

A lipoprotein of Yersinia enterocolitica facilitates ferrioxamine uptake in Escherichia coli

A lipoprotein of Yersinia enterocolitica facilitates ferrioxamine uptake in Escherichia coli

Pattern searches for the identification of putative lipoprotein genes in Gram-positive bacterial genomes

A Lipid‐Anchored Binding Protein is a Component of an ATP‐Dependent Cellobiose/Cellotriose‐Transport System from the Cellulose Degrader Streptomyces reticuli

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