Department of Microbiology and Immunology and Medicine, University of Western Ontario, London, Ontario, N6A 5C1, Canada1
Zentrum für Ultrastrukturforschung und Ludwig Boltzmann-Institut für Molekulare Nanotechnologie, Universität für Bodenkultur Wien, A-1180 Wien, Austria2
Institut für Chemie, Universität für Bodenkultur Wien, A-1190 Wien, Austria3
Author for correspondence: Miguel A. Valvano. Tel: +1 519 661 3996. Fax: +1 519 661 3499. e-mail: mvalvano{at}uwo.ca
Keywords: lipopolysaccharide, sugar kinase, sugar phosphate phosphatase, surface layer (S-layer), capsules
![]() |
Overview |
---|
|
![]() |
Importance of heptose residues in cell surface polysaccharides and bacterial glycoproteins |
---|
LPS plays an important role in maintaining the structural integrity of the bacterial outer membrane by interacting with outer-membrane proteins as well as divalent cations (Ferguson et al., 2000 ; Hancock et al., 1994
). Phosphate groups covalently attached to heptose residues in the inner core participate in these ionic interactions, which provide a barrier preventing the passage of hydrophobic substances such as detergents, dyes and antibiotics across the outer membrane (Nikaido, 1994
; Nikaido & Vaara, 1985
). E. coli mutants lacking heptose in the LPS display hypersensitivity to novobiocin, detergents and bile salts (Tamaki et al., 1971
). They also have defects in F plasmid conjugation and generalized transduction by the bacteriophage P1 (Curtiss et al., 1968
; Havekes et al., 1976
; Sherburne & Taylor, 1997
). These phenotypes are associated with a reduced amount of outer-membrane proteins, some of which serve as surface receptors for conjugation and bacteriophage attachment (Bayer et al., 1975
; Koplow & Goldfine, 1974
; Sherburne & Taylor, 1997
; Vakharia & Misra, 1996
; van Alphen et al., 1976
; Verkleij et al., 1976
) or as channel components of efflux systems (Fralick & Burns-Keliher, 1994
; Koronakis et al., 1997
). The reduced stability of the outer membrane in these mutants is associated at least in part with the absence of phosphate groups, since mutations in genes encoding LPS core kinases also show pleiotropic phenotypes similar to those found in heptose-deficient mutants (Yethon & Whitfield, 2001
; Yethon et al., 2000
). Usually LPS heptose-deficient mutants in many bacterial species can survive in the laboratory. However, in some micro-organisms like Pseudomonas aeruginosa, heptoseless mutants have not been isolated and it has been proposed that these residues (or the phosphates covalently attached to them) are essential for bacterial survival in vitro (Walsh et al., 2000
). Heptose-deficient mutants are generally serum-sensitive and display reduced virulence in experimental infection models (Helander et al., 1988
; Zwahlen et al., 1985
).
Many bacterial species are characterized by the production of regular protein surface arrays known as S-layers (Messner & Sleytr, 1992 ; Sára & Sleytr, 2000
; Sleytr & Messner, 2000
). Recent work has revealed that some S-layer proteins are glycosylated (Messner & Sleytr, 1991
; Messner & Schäffer, 2002
; Schäffer et al., 2001
; Sumper & Wieland, 1995
). glycero-manno-Heptose is one of the sugar components of the disaccharide repeating unit of the well-characterized S-layer glycan in Aneurinibacillus thermoaerophilus DSM 10155 (Kosma et al., 1995
; Wugeditsch et al., 1999
). Protein glycosylation in prokaryotes is not only limited to S-layer proteins. Pilins, non-piliated adhesins, flagellar filament subunits and secreted exoenzymes in a variety of archaeal and eubacterial micro-organisms are modified by the addition of carbohydrate residues (Messner & Schäffer, 2002
; Schäffer et al., 2001
). Glycosylation with glycero-manno-heptose residues has been demonstrated in the AIDA-I autotransporter adhesin of diarrhoeagenic E. coli (Benz & Schmidt, 2001
). This modification not only improved the stability of the adhesin but also was essential for the adherent function of the protein (Benz & Schmidt, 2001
). Thus glycosylation of bacterial surface proteins may serve a number of functions, including adherence, evasion of host immune responses, and an enhanced resistance to proteolytic attack.
![]() |
A novel kinase/phosphatase cascade is involved in the biosynthesis of nucleotide-activated glycero-manno-heptose |
---|
More recently, it was demonstrated that the E. coli hldE gene (formerly rfaE, see below) encodes a bifunctional protein with two distinct functional domains that may be involved in the biosynthesis of D,D-heptose 1-phosphate as well as the activating step (Valvano et al., 2000 ). One of the HldE domains shares structural features with members of the ribokinase family, while the other domain has conserved features present in nucleotidyltransferases (Valvano et al., 2000
). The demonstration of a protein domain corresponding to a putative sugar kinase suggested a different process for nucleotide-activated heptose biosynthesis than the one proposed by Eidels and Osborn and, at the same time, predicted the existence of an additional phosphatase step (Valvano, 1999
). A kinase/phosphatase cascade in place of a mutase step was biochemically confirmed following the complete elucidation of the biosynthesis pathway for GDP-D-glycero-
-D-manno-heptose in the Gram-positive bacterium A. thermoaerophilus (Kneidinger et al., 2001
) and for ADP-L-glycero-ß-D-manno-heptose in E. coli (Kneidinger et al., 2002
). These novel steps revealed a major difference from the majority of the classical pathways leading to the formation of nucleotide-activated sugars, which usually involve a mutase step catalysing the intramolecular transfer of a phosphate group from the distal carbon to the C-1 position. This phosphate is subsequently modified to form a phosphodiester linkage with the nucleotide by a nucleotidylyltransferase, which results in the synthesis of a nucleotide diphosphate-sugar precursor.
Furthermore, the kinase enzymes determine the anomeric specificity of the diphosphate reaction products, and, as expected, the nucleotidylyltransferases are also specific for the anomeric form of the D,D-heptose 1-phosphate that results from the phosphatase step (Kneidinger et al., 2002 ). The GDP-activated heptose serves as a precursor for the glycan moiety of A. thermoaerophilus S-layer glycoprotein, which consists of
-L-rhamnose and D-glycero-ß-D-manno-heptose residues (M. Graninger, B. Kneidinger, K. Bruno & P. Messner, unpublished results; Kneidinger et al., 2001
; Kosma et al., 1995
). In contrast, the ADP-activated heptose serves as a substrate for the glycosyltransferases involved in the assembly of the LPS inner-core oligosaccharide (Gronow et al., 2001
; Zamyatina et al., 2000
). Two different biosynthetic pathways, which we have named the D-
-D-heptose and the L-ß-D-heptose pathways (Fig. 1
), can be distinguished on the basis of the specificity of the kinase and the nucleotidylyltransferase steps. The isomerase and phosphatase enzymes are common to both pathways and their functions are independent of the anomeric conformation of the sugar phosphate substrates. Thus these enzymes are conserved in a wide range of Gram-positive and Gram-negative bacteria. We have proposed a rational gene nomenclature to account for the differences and similarities between the two pathways (Kneidinger et al., 2002
) (Table 1
). In the sections that follow, we describe the characteristics of the enzymes involved in the biosynthesis pathways for nucleotide-activated heptose.
|
![]() |
Common steps in the biosynthesis pathways of nucleotide-activated heptose |
---|
Inspection of sequenced bacterial genomes reveals that GmhA is highly conserved in many Gram-negative bacteria as well as in some Gram-positive micro-organisms, such as A. thermoaerophilus and Clostridium acetobutylicum, and also in Mycobacterium tuberculosis. The homologue from Haemophilus influenzae has been cloned and shown to complement the E. coli gmhA (formerly lpcA) mutation (Brooke & Valvano, 1996a ). GmhA has amino acid sequence conservation with the C-terminal region of L-glutamine:D-fructose-6-phosphate amidotransferases, which are also ketose/aldose isomerases (Golinelli-Pimpaneau et al., 1989
). All of these proteins share a domain termed the sugar isomerase (SIS) domain (Bateman, 1999
). The C-terminal isomerase domain of the E. coli glucosamine-6-phosphate synthase (GlmS) has been crystallized in the presence of glucosamine 6-phosphate and shown to consist of two topologically identical subdomains of equal size. Each of these domains is characterized by an
ß
motif that represents the nucleotide-binding motif of a flavoredoxin type (Teplyakov et al., 1998
). The amino acid conservation with GmhA proteins is particularly strong, especially with three serine residues and a threonine of GlmS that form hydrogen bonds with the phosphate group of glucosamine 6-phosphate (Teplyakov et al., 1998
). These residues presumably interact with the phosphate group of sedoheptulose 7-phosphate or D-glycero-D-manno-heptose 7-phosphate and they are universally conserved in all GmhA homologues (Fig. 2
).
|
|
![]() |
D-![]() |
---|
|
|
![]() |
L-ß-D-Heptose pathway |
---|
The E. coli hldE gene encodes a polypeptide of approximately 55 kDa, and comparisons of the predicted amino acid sequence with other proteins in the database showed the presence of two clearly separate domains (Valvano et al., 2000 ). The N-terminal domain I, which spans amino acids 1318, shares structural features with members of the ribokinase family. This is a large family of proteins whose function is the phosphorylation of sugars at positions 1 or 6 in the case of hexoses, and 1 or 5 in the case of pentoses (Bork et al., 1993
; Sigrell et al., 1998
). The C-terminal domain II, which spans amino acids 344477, has all the conserved features of the cytidylyltransferase superfamily (Bork et al., 1995
), including the aut gene product of Ralstonia (formerly Alcaligenes) eutropha (Freter & Bowien, 1994
; Valvano et al., 2000
). Two members of the cytidylyltransferase superfamily, pantoateß-alanine ligase and acetate:SH-citrate lyase, are ATP transferases (Bork et al., 1995
). Also, all the members in this family have structural conservation with the class I tRNA synthetases, which are also ATP transferases (Bork et al., 1995
). By subcloning and expressing each domain separately, we showed that domain I was sufficient to complement the rfaE mutation in Sal. enterica (Valvano et al., 2000
). We also showed that the aut::Tn5 mutation in R. eutropha determines a heptose-deficient LPS phenotype, which can be complemented only with the expressed domain II. The aut mutation has been associated with pleiotropic effects, including autotrophic growth, and changes in cell morphology and colony appearance (Freter & Bowien, 1994
). A comparison of the LPS electrophoretic profile of this mutant with the wild-type strain revealed that the mutant has a fast-migrating lipid Acore band that co-migrates with that of the E. coli heptose-deficient lipid Acore. Also, the mutant is novobiocin-sensitive while the wild-type strain is resistant to this antibiotic. These experiments demonstrated that both domains of the E. coli gene are functionally different, suggesting that the HldE polypeptide is bifunctional. The bifunctional nature of this enzyme was recently demonstrated in vitro using purified components of the nucleotide-activated heptose pathway (Kneidinger et al., 2002
). Based on genomic sequence comparisons, similar bifunctional proteins are predicted to be present in several Gram-negative micro-organisms, including Ha. influenzae, He. pylori, Vibrio cholerae and Ps. aeruginosa. In contrast, individual genes encoding domains I and II independently are found in R. eutropha, Neisseria meningitidis and Neisseria gonorrhoeae. In these cases, we propose to use the nomenclature hldA and hldC to indicate the individual kinase- and adenylyltransferase-encoding genes, respectively (Table 1
, see below).
HldD ADP-L-glycero-D-manno-heptose 6-epimerase
The ADP-L-glycero-D-manno-heptose 6-epimerase, which is encoded by the hldD (formerly waaD or rfaD, see Table 1) gene, has been well characterized. The function of this enzyme in E. coli was determined by Coleman (1983)
using chromatographic and mass-spectroscopic methods to examine the heptose components of LPS extracted from the gmhD mutant. This epimerization reaction is the last enzymic step required for the synthesis of ADP-L-glycero-D-manno-heptose. The epimerization occurs at the C-6 position of the heptose and involves an oxidationreduction process that requires NADP+ as a cofactor (Ni et al., 2001
). HldD has a high structural similarity with UDP-galactose epimerase and it has been classified as a member of the short-chain dehydrogenase/reductase (SDR) superfamily (Deacon et al., 2000
). The enzyme is a homopentamer and each monomer is composed of two domains. The large N-terminal domain consists of a modified seven-stranded Rossmann fold which contains the characteristic sequence Gly-Gly-X-Gly-X-X-Gly (Pegues et al., 1990
; Wierenga et al., 1986
) and is associated with NADP binding (Deacon et al., 2000
). The C-terminal domain has an
/ß structure that is involved in substrate binding.
![]() |
Gene organization of heptose biosynthesis pathways |
---|
In the majority of bacterial genomes sequenced to date, the genes encoding the enzymes of the L-ß-D-heptose pathway are scattered throughout the chromosome. This is particularly true for the enteric as well as non-enteric bacteria like Ha. influenzae, Ps. aeruginosa, V. cholerae, He. pylori, N. meningitidis, N. gonorrhoeae and others. In most genomes examined, HldE is encoded as a bifunctional enzyme. However, in N. meningitidis, N. gonorrhoeae and R. eutropha, the two domains of the HldE protein are encoded by separate genes, hldA (kinase) and hldC (adenylyltransferase). The hldD gene is the only gene consistently found within core oligosaccharide biosynthesis clusters, usually in association with heptosyltransferase genes, like waaE and/or waaF (Fig. 5), which are known to process the ß-anomers of ADP-L-glycero-D-manno-heptose (Gronow et al., 2001
; Zamyatina et al., 2000
). In some micro-organisms like Ca. jejuni and Mesorhizobium loti, all L-ß-D-heptose biosynthesis genes are found clustered (Fig. 5
), and the neighbouring genes are also involved in LPS core biosynthesis. In contrast, the four genes for L-ß-D-heptose biosynthesis in He. pylori 26695 are part of a large cluster that also includes a flagellin gene, which suggests the intriguing possibility that the flagellin in this strain may be glycosylated.
The genes for the D--D-heptose pathway were first described in A. thermoaerophilus DSM 10155, where they are located within a cluster containing additional genes involved in the synthesis and transfer of dTDP-rhamnose (Fig. 5
). Since dTDP-rhamnose is also a component of the S-layer glycan moiety in A. thermoaerophilus DSM 10155 (M. Graninger, B. Kneidinger, K. Bruno & P. Messner, unpublished results; Kneidinger et al., 2001
; Kosma et al., 1995
), the gene cluster may be involved in protein glycosylation. These genes are also present in My. tuberculosis, albeit in two different locations (Fig. 4
), where they may be involved in the synthesis of glycolipids or in protein glycosylation (Romain et al., 1999
). Interestingly, in the case of My. tuberculosis strain CDC 1551, the gmhB and gmhA appeared to be fused as a single gene, probably encoding a bifunctional protein with phosphatase and isomerase activities (Table 2
). In the Gram-positive anaerobe Cl. acetobutylicum and in the Gram-negatives Ca. jejuni, B. mallei and B. pseudomallei, the D-
-D-heptose pathway genes are present within a large cluster with a gene organization resembling group II capsule genes (Fig. 5
). B. pseudomallei produces an exopolysaccharide made of unbranched 2-O-acetyl-6-deoxy-ß-D-manno-heptopyranose (Reckseidler et al., 2001
). The repeating units of several Ca. jejuni O polysaccharides contain several variants on heptose residues, including D-glycero-D-altro-heptose or modifications of this molecule through methylation, deoxygenation or both (Penner & Aspinall, 1997
). Interestingly, genes encoding putative methyltransferases and epimerase/dehydratases are also present within this group II capsule-like cluster in Ca. jejuni (Dorrell et al., 2001
). Further research is required to determine whether these rare heptoses arise from precursors of the D-
-D-heptose or the L-ß-D-heptose pathways.
|
![]() |
Future areas of research |
---|
![]() |
ACKNOWLEDGEMENTS |
---|
![]() |
REFERENCES |
---|
Aspinall, G. O., Monteiro, M. A., Shaver, R. T., Kurjanczyk, L. A. & Penner, J. L. (1997). Lipopolysaccharides of Helicobacter pylori serogroups O:3 and O:6. Eur J Biochem 248, 592-601.[Abstract]
Bateman, A. (1999). The SIS domain: a phosphosugar-binding domain. Trends Biochem Sci 24, 94-95.[Medline]
Bayer, M. E., Koplow, J. & Goldfine, H. (1975). Alterations in envelope structure of heptose-deficient mutants of Escherichia coli as revealed by freeze-etching. Proc Natl Acad Sci USA 72, 5145-5149.[Abstract]
Benz, I. & Schmidt, M. A. (2001). Glycosylation with heptose residues mediated by the aah gene product is essential for adherence of the AIDA-I adhesin. Mol Microbiol 40, 1403-1413.[Medline]
Bork, P., Sander, C. & Valencia, A. (1993). Convergent evolution of similar enzymatic function on different protein folds: the hexokinase, ribokinase, and galactokinase families of sugar kinases. Protein Sci 2, 31-40.
Bork, P., Holm, L., Koonin, E. V. & Sander, C. (1995). The cytidylyltransferase superfamily: identification of the nucleotide-binding site and fold prediction. Proteins 22, 259-266.[Medline]
Brooke, J. S. (1996). Characterization of a phosphoheptose isomerase involved in inner core lipopolysaccharide biosynthesis. PhD Dissertation, University of Western Ontario.
Brooke, J. S. & Valvano, M. A. (1996a). Molecular cloning of the Haemophilus influenzae gmhA (lpcA) gene encoding a phosphoheptose isomerase required for lipooligosaccharide biosynthesis. J Bacteriol 178, 3339-3341.[Abstract]
Brooke, J. S. & Valvano, M. A. (1996b). Biosynthesis of inner core lipopolysaccharide in enteric bacteria identification and characterization of a conserved phosphoheptose isomerase. J Biol Chem 271, 3608-3614.
Burtnick, M. N. & Woods, D. E. (1999). Isolation of polymyxin B-susceptible mutants of Burkholderia pseudomallei and molecular characterization of genetic loci involved in polymyxin B resistance. Antimicrob Agents Chemother 43, 2648-2656.
Coleman, W. G.Jr (1983). The rfaD gene codes for ADP-L-glycero-D-mannoheptose-6-epimerase. An enzyme required for lipopolysaccharide core biosynthesis. J Biol Chem 258, 1985-1990.
Collet, J.-F., Stroobant, V., Pirard, M., Delpierre, G. & Van Schaftingen, E. (1998). A new class of phosphotransferases phosphorylated on an aspartate residue in an amino-terminal DXDX(T/V) motif. J Biol Chem 273, 14107-14112.
Curtiss, R., Charamella, J., Stallions, D. R. & Mays, J. A. (1968). Parental functions during conjugation. Bacteriol Rev 32, 320-348.[Medline]
Czaja, J., Jachymek, W., Niedzela, T., Lugowski, C., Aldova, E. & Kenne, L. (2000). Structural studies of the O-specific polysaccharide from Plesiomonas shigelloides strain CNCTC 113/92. Eur J Biochem 267, 1672-1679.
Deacon, A. M., Ni, Y. S., Coleman, W. G.Jr & Ealick, S. E. (2000). The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist. Structure 8, 453-462.[Medline]
DeShazer, D., Waag, D. M., Fritz, D. L. & Woods, D. E. (2001). Identification of a Burkholderia mallei polysaccharide gene cluster by subtractive hybridization and demonstration that the encoded capsule is an essential virulence determinant. Microb Pathog 30, 253-269.[Medline]
Dorrell, N., Mangan, J. A., Laing, K. G. & 9 other authors (2001). Whole genome comparison of Campylobacter jejuni human isolates using a low-cost microarray reveals extensive genetic diversity. Genome Res 11, 17061715.
Eidels, L. & Osborn, M. J. (1971). Lipopolysaccharide and aldoheptose biosynthesis in transketolase mutants of Salmonella typhimurium. Proc Natl Acad Sci USA 68, 1673-1677.[Abstract]
Eidels, L. & Osborn, M. J. (1974). Phosphoheptose isomerase, first enzyme in the biosynthesis of aldoheptose in Salmonella typhimurium. J Biol Chem 249, 5642-5648.
Eidels, L., Rick, P. D., Stimler, N. P. & Osborn, M. J. (1974). Transport of D-arabinose-5-phosphate and D-sedoheptulose-7-phosphate by the hexose phosphate transport system of Salmonella typhimurium. J Bacteriol 119, 138-143.[Medline]
Ferguson, A. D., Welte, W., Hofmann, E., Lindner, B., Holst, O., Coulton, J. W. & Diederichs, K. (2000). A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins. Structure Fold Des 8, 585-592.[Medline]
Fralick, J. A. & Burns-Keliher, L. L. (1994). Additive effect of tolC and rfa mutations on the hydrophobic barrier of the outer membrane of Escherichia coli K-12. J Bacteriol 176, 6404-6406.[Abstract]
Freter, A. & Bowien, O. (1994). Identification of a novel gene, aut, involved in autotrophic growth of Alcaligenes eutrophus. J Bacteriol 176, 5401-5408.[Abstract]
Golinelli-Pimpaneau, B., Le Goffic, F. & Badet, B. (1989). Glucosamine-6-phosphate from Escherichia coli: mechanism of the reaction at the fructose-6-phosphate binding site. J Am Chem Soc 111, 3029-3034.
Gronow, S., Oertelt, C., Ervelä, E., Zamyatina, A., Kosma, P., Skurnik, M. & Holst, O. (2001). Characterization of the physiological substrate for lipopolysaccharide heptosyltransferases I and II. J. Endotoxin Res 7, 263-270.[Medline]
Hancock, R. E. W., Karunaratne, D. N. & Bernegger-Egli, C. (1994). Molecular organization and structural role of outer membrane macromolecules. In Bacterial Cell Wall , pp. 263-279. Edited by J. M. Ghuysen & R. Hackenbeck. Amsterdam & New York: Elsevier.
Havekes, L. M., Lugtenberg, B. J. J. & Hoekstra, W. P. M. (1976). Conjugation deficient E. coli K-12 F- mutants with heptose-less lipopolysaccharide. Mol Gen Genet 146, 43-50.[Medline]
Heinrichs, D. E., Valvano, M. A. & Whitfield, C. (1999). Biosynthesis and genetics of lipopolysaccharide core. In Endotoxin in Health and Disease , pp. 305-330. Edited by H. Brade, D. C. Morrison, S. Vogel & S. Opal. New York: Marcel Dekker.
Helander, I. M., Lindner, B., Brade, H., Altmann, K., Lindberg, A. A., Rietschel, E. T. & Zahringer, U. (1988). Chemical structure of the lipopolysaccharide of Haemophilus influenzae strain I-69 Rd-/B+: description of a novel deep-rough chemotype. Eur J Biochem 177, 483-492.[Abstract]
Hisano, T., Hata, Y., Fujii, T., Liu, J.-Q., Kurihara, T., Esaki, N. & Soda, K. (1996). Crystal structure of L-2-haloacid dehalogenase from Pseudomonas sp. YL. An /ß hydrolase structure that is different from the
/ß hydrolase fold. J Biol Chem 271, 20322-20330.
Holst, O., Zahringer, U., Brade, H. & Zamojski, A. (1991). Structural analysis of the heptose/hexose region of the lipopolysaccharide from Escherichia coli K-12 strain W3100. Carbohydr Res 215, 323-335.[Medline]
Jachymek, W., Niedzela, T., Petersson, C., Lugowski, C., Czaja, J. & Kenne, L. (1999). Structures of the O-specific polysaccharides from Yokenella regensburgei (Koserella trabulsii) strains PCM 2476, 2477, 2478, and 2494: high-resolution magic angle spinning NMR investigation of the O-specific polysaccharides in native lipopolysaccharides and directly on the surface of living bacteria. Biochemistry 38, 11788-11795.[Medline]
Kadrmas, J. L., Brozek, K. A. & Raetz, C. R. H. (1996). Lipopolysaccharide core glycosylation in Rhizobium leguminosarum. An unusual mannosyl transferase resembling the heptosyl transferase I of Escherichia coli. J Biol Chem 271, 32119-32125.
Kawahara, K., Brade, H., Rietschel, E. T. & Zähringer, U. (1987). Studies on the chemical structure of the core-lipid A region of the lipopolysaccharide of Acinetobacter calcoaceticus NCTC 10305. Eur J Biochem 163, 489-495.[Abstract]
Kneidinger, B., Graninger, M., Puchberger, M., Kosma, P. & Messner, P. (2001). Biosynthesis of nucleotide-activated D-glycero-D-manno-heptose. J Biol Chem 276, 20935-20944.
Kneidinger, B., Marolda, C. L., Graninger, M., Zamyatina, A., McArthur, F., Kosma, P., Valvano, M. A. & Messner, P. (2002). Biosynthesis pathway of ADP-D-glycero-L-manno-heptose in Escherichia coli. J Bacteriol 184, 363-369.
Knirel, Y. A., Moll, H. & Zähringer, U. (1996). Structural study of a highly O-acetylated core of Legionella pneumophila serogroup 1 lipopolysaccharide. Carbohydr Res 293, 223-234.[Medline]
Kocsis, B. & Kontrohr, T. (1984). Isolation of adenosine 5'-diphosphate-L-glycero-D-mannoheptose, the assumed substrate of heptose transferase(s), from Salmonella minnesota R595 and Shigella sonnei Re mutants. J Biol Chem 259, 11858-11860.
Koonin, E. V. & Tatusov, R. L. (1994). Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search. J Mol Biol 244, 125-132.[Medline]
Koplow, J. & Goldfine, H. (1974). Alterations in the outer membrane of the cell envelope of heptose-deficient mutants of Escherichia coli. J Bacteriol 117, 527-543.[Medline]
Koronakis, V., Koronakis, E., Li, J. & Stauffer, K. (1997). Structure of TolC, the outer membrane component of the bacterial type I efflux system, derived from two-dimensional crystals. Mol Microbiol 23, 617-626.[Medline]
Kosma, P., Wugeditsch, T., Christian, R., Zayni, S. & Messner, P. (1995). Glycan structure of a heptose-containing S-layer glycoprotein of Bacillus thermoaerophilus. Glycobiology 5, 791-796.[Abstract]
Melaugh, W., Phillips, N. J., Campagnari, A. A., Karalus, R. & Gibson, B. W. (1992). Partial characterization of the major lipooligosaccharide from a strain of Haemophilus ducreyi, the causative agent of chancroid, a genital ulcer disease. J Biol Chem 267, 13434-13439.
Messner, P. & Schäffer, C. (2002). Prokaryotic glycoproteins. In Progress in the Chemistry of Organic Natural Compounds, vol. 85. Edited by W. Herz, G. Falk, G. W. Kirby, R. E. Moore & C. Tamm. Wien: Springer-Verlag (in press).
Messner, P. & Sleytr, U. B. (1991). Bacterial surface layer glycoproteins. Glycobiology 1, 545-551.[Abstract]
Messner, P. & Sleytr, U. B. (1992). Crystalline bacterial cell-surface layers. Adv Microb Physiol 33, 213-275.[Medline]
Ni, Y., McPhie, P., Deacon, A., Ealick, S. E. & Coleman, W. G.Jr (2001). Evidence that NADP+ is the physiological cofactor of ADP-L-glycero-D-mannoheptose 6-epimerase. J Biol Chem 276, 27329-27334.
Nikaido, H. (1994). Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264, 382-388.[Medline]
Nikaido, H. & Vaara, M. (1985). Molecular basis of bacterial outer membrane permeability. Microbiol Rev 49, 1-32.
Pegues, J. C., Chen, L. S., Gordon, A. W., Ding, L. & Coleman, W. G.Jr (1990). Cloning, expression, and characterization of the Escherichia coli K-12 rfaD gene. J Bacteriol 172, 4652-4660.[Medline]
Penner, J. L. & Aspinall, G. O. (1997). Diversity of lipopolysaccharide structures in Campylobacter jejuni. J Infect Dis 176 (Suppl. 2), S135S138.
Raetz, C. R. H. (1996). Bacterial lipopolysaccharides: a remarkable family of bioactive molecules. In Escherichia coli and Salmonella: Cellular and Molecular Biology, pp. 10351063. Edited by F. C. Neidhardt and others. Washington, DC: American Society for Microbiology.
Reckseidler, S. L., DeShazer, D., Sokol, P. A. & Woods, D. E. (2001). Detection of bacterial virulence genes by subtractive hybridization: identification of capsular polysaccharide of Burkholderia pseudomallei as a major virulence determinant. Infect Immun 69, 34-44.
Reeves, P. R., Hobbs, M., Valvano, M. A. & 8 other authors (1996). Bacterial polysaccharide synthesis and gene nomenclature. Trends Microbiol 4, 495503.[Medline]
Regue, M., Climent, N., Abitiu, N., Coderch, N., Merino, S., Izquierdo, L., Altarriba, M. & Tomas, J. M. (2001). Genetic characterization of the Klebsiella pneumoniae waa gene cluster, involved in core lipopolysaccharide biosynthesis. J Bacteriol 183, 3564-3573.
Ridder, I. S., Rozeboom, H. J., Kalk, K. H., Janssen, D. B. & Dijkstra, B. W. (1997). Three-dimensional structure of L-2-haloacid dehalogenase from Xanthobacter autotrophicus GJ10 complexed with the substrate-analogue formate. J Biol Chem 272, 33015-33022.
Romain, F., Horn, C., Pescher, P., Namane, A., Riviere, M., Puzo, G., Barzu, O. & Marchal, G. (1999). Deglycosylation of the 45/47-kilodalton antigen complex of Mycobacterium tuberculosis decreases its capacity to elicit in vivo or in vitro cellular immune responses. Infect Immun 67, 5567-5572.
Rossmann, M. G., Moras, D. & Olsen, K. W. (1974). Chemical and biological evolution of nucleotide-binding protein. Nature 250, 194-199.[Medline]
Sára, M. & Sleytr, U. B. (2000). S-layer proteins. J Bacteriol 182, 859-868.
Schäffer, C., Graninger, M. & Messner, P. (2001). Prokaryotic glycosylation. Proteomics 1, 248-261.[Medline]
Sherburne, C. & Taylor, D. E. (1997). Effect of lipopolysaccharide mutations on recipient ability of Salmonella typhimurium for incompatibility group H plasmids. J Bacteriol 179, 952-955.[Abstract]
Shih, G. C., Kahler, C. M., Carlson, R. l. W., Rahman, M. M. & Stephens, D. S. (2001). gmhX, a novel gene required for the incorporation of L-glycero-D-manno-heptose into lipooligosaccharide in Neisseria meningitidis. Microbiology 147, 2367-2377.
Sigrell, J. A., Cameron, A. D., Jones, T. A. & Mowbray, S. L. (1998). Structure of Escherichia coli ribokinase in complex with ribose and dinucleotide determined to 1·8 resolution: insights into a new family of kinase structures. Structure 6, 183-193.[Medline]
Sirisena, D. M., Brozek, K. A., MacLachlan, P. R., Sanderson, K. E. & Raetz, C. R. (1992). The rfaC gene of Salmonella typhimurium. Cloning, sequencing, and enzymatic function in heptose transfer to lipopolysaccharide. J Biol Chem 267, 18874-18884.
Sleytr, U. B. & Messner, P. (2000). Crystalline bacterial cell surface layers (S layers). In Encyclopedia of Microbiology , pp. 899-906. Edited by J. Lederberg. San Diego, CA: Academic Press.
Sozhamannan, S., Deng, Y. K., Li, M., Sulakvelidze, A., Kaper, J. B., Johnson, J. A., Nair, G. B. & Morris, J. G.Jr (1999). Cloning and sequencing of the genes downstream of the wbf gene cluster of Vibrio cholerae serogroup O139 and analysis of the junction genes in other serogroups. Infect Immun 67, 5033-5040.
Sumper, M. & Wieland, F. T. (1995). Bacterial glycoproteins. In Glycoproteins , pp. 455-473. Edited by J. Montreuil, J. F. G. Vliegenthart & H. Schachter. Amsterdam: Elsevier.
Süsskind, M., Brade, L., Brade, H. & Holst, O. (1998). Identification of a novel heptoglycan of alpha12-linked D-glycero-D-manno-heptopyranose. J Biol Chem 273, 7006-7017.
Tamaki, S., Sato, T. & Matsuhashi, M. (1971). Role of lipopolysaccharides in antibiotic resistance and bacteriophage adsorption of Escherichia coli K-12. J Bacteriol 105, 968-975.[Medline]
Teplyakov, A., Obmolova, G., Badet-Denisot, M. A., Badet, B. & Polikarpov, I. (1998). Involvement of the C terminus in intramolecular nitrogen channeling in glucosamine 6-phosphate synthase: evidence from a 1·6 crystal structure of the isomerase domain. Structure 6, 1047-1055.[Medline]
Thibault, P., Logan, S. M., Kelly, J. F., Brisson, J.-R., Ewing, C. P., Trust, T. J. & Guerry, P. (2001). Identification of the carbohydrate moieties and glycosylation motifs in Campylobacter jejuni flagellin. J Biol Chem 276, 34862-34870.
Vakharia, H. & Misra, R. (1996). A genetic approach for analysing surface-exposed regions of the OmpC protein of Escherichia coli K-12. Mol Microbiol 19, 881-889.[Medline]
Valvano, M. A. (1999). Biosynthesis and genetics of ADP-heptose. J Endotoxin Res 5, 90-95.
Valvano, M. A., Marolda, C. L., Bittner, M., Glaskin-Clay, M., Simon, T. L. & Klena, J. D. (2000). The rfaE gene from Escherichia coli encodes a bifunctional protein involved in the biosynthesis of the lipopolysaccharide core precursor ADP-L-glycero-D-manno-heptose. J Bacteriol 182, 488-497.
van Alphen, W., Lugtenberg, B. & Berendsen, W. (1976). Heptose-deficient mutants of Escherichia coli K12 deficient in up to three major outer membrane proteins. Mol Gen Genet 147, 263-269.[Medline]
Verkleij, A. J., Lugtenberg, E. J. & Ververgaert, P. H. (1976). Freeze etch morphology of outer membrane mutants of Escherichia coli K12. Biochim Biophys Acta 426, 581-586.[Medline]
Walsh, A. G., Matewish, M. J., Burrows, L. L., Monteiro, M. A., Perry, M. B. & Lam, J. S. (2000). Lipopolysaccharide core phosphates are required for viability and intrinsic drug resistance in Pseudomonas aeruginosa. Mol Microbiol 35, 718-727.[Medline]
Wang, W., Kim, R., Jancarik, J., Yokota, H. & Kim, S. (2001). Crystal structure of phosphoserine phosphatase from Methanococcus jannaschii, a hyperthermophile, at 1·8 resolution. Structure 9, 65-72.[Medline]
Whitfield, C. & Valvano, M. A. (1993). Biosynthesis and expression of cell-surface polysaccharides in gram-negative bacteria. Adv Microb Physiol 35, 135-246.[Medline]
Wierenga, R. K., Terpstra, P. & Hol, W. G. (1986). Prediction of the occurrence of the ADP-binding ßß-fold in proteins, using an amino acid sequence fingerprint. J Mol Biol 187, 101-107.[Medline]
Wugeditsch, T., Zachara, N. E., Puchberger, M., Kosma, P., Gooley, A. A. & Messner, P. (1999). Structural heterogeneity in the core oligosaccharide of the S-layer glycoprotein from Aneurinibacillus thermoaerophilus DSM 10155. Glycobiology 9, 787-795.
Yethon, J. A. & Whitfield, C. (2001). Purification and characterization of WaaP from Escherichia coli, a lipopolysaccharide kinase essential for outer membrane stability. J Biol Chem 276, 5498-5504.
Yethon, J. A., Vinogradov, E., Perry, M. B. & Whitfield, C. (2000). Mutation of the lipopolysaccharide core glycosyltransferase encoded by waaG destabilizes the outer membrane of Escherichia coli by interfering with core phosphorylation. J Bacteriol 182, 5620-5623.
Zamyatina, A., Gronow, S., Oertelt, C., Puchberger, M., Brade, H. & Kosma, P. (2000). Efficient chemical synthesis of the two anomers of ADP-L-glycero- and D-glycero-D-manno-heptopyranose allows the determination of substrate specificities of bacterial heptosyltransferases. Angew Chem Int Ed 39, 4150-4153.
Zhou, T., Daugherty, M., Grishin, N. V., Osterman, A. L. & Zhang, H. (2000). Structure and mechanism of homoserine kinase: prototype for the GHMP kinase superfamily. Structure 8, 1247-1257.[Medline]
Zwahlen, A., Rubin, L. G., Connelly, C. J., Inzana, T. J. & Moxon, E. R. (1985). Alteration of the cell wall in Haemophilus influenzae type b by transformation with cloned DNA: association with attenuated virulence. J Infect Dis 152, 485-492.[Medline]