Isolation and characterisation of disodium (4-amino-4-deoxy-β-l-arabinopyranosyl)-(1⃗8)-(d-glycero-α-d-talo-oct-2-ulopyranosylonate)-(2⃗4)-(methyl 3-deoxy-d-manno-oct-2-ulopyranosid)onate from the lipopolysaccharide of Burkholderia cepacia

Isshiki, Yasunori; Kawahara, Kazuyoshi; Zähringer, Ulrich

doi:10.1016/s0008-6215(98)00179-7

Cited by 68 publications

(63 citation statements)

References 22 publications

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“…We suggest that the OH group incorporated by KdoO at the 3-position has the axial configuration based on previous 1 H-NMR analyses of Ko (Fig. 1A) (10). However, NMR studies of the product generated in vitro by KdoO will be required to establish this stereochemistry with certainty.…”

Section: Resultsmentioning

confidence: 68%

“…In many strains of Yersinia and Burkholderia, Ko replaces the distal Kdo unit of the Kdo disaccharide in LPS (10)(11)(12)(13)(14). We hypothesized that Ko might be derived from Kdo by an enzymatic hydroxylation reaction (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, in our E. coli constructs, there is no effect of KdoO expression on bile salt, polymyxin, or calcium sensitivity. In Burkholderia cenocepacia, one 4-amino-4-deoxy-L-arabinose unit is linked to the Ko moiety of the core, possibly providing additional resistance to cationic antimicrobial peptides (10). The enzyme responsible for 4-amino-4-deoxy-L-arabinose addition to Ko is unknown, but it might require the prior conversion of Kdo to Ko for its activity.…”

Section: Discussionmentioning

confidence: 99%

“…Yersinia pestis causes "Bubonic Plague" in humans (9). These important Gram-negative pathogens synthesize an unusual isosteric analog of Kdo, known as D-glycero-D-talo-oct-2-ulosonic acid (Ko) (10)(11)(12)(13)(14) in which the axial hydrogen atom at the 3-position of the outer Kdo unit is replaced with an OH group (10) (Fig. 1A).…”

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confidence: 99%

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Dioxygenases in Burkholderia ambifaria and Yersinia pestis that hydroxylate the outer Kdo unit of lipopolysaccharide

Chung

Raetz

2010

Proc. Natl. Acad. Sci. U.S.A.

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Several Gram-negative pathogens, including Yersinia pestis, Burkholderia cepacia , and Acinetobacter haemolyticus , synthesize an isosteric analog of 3-deoxy- d - manno -oct-2-ulosonic acid (Kdo), known as d -glycero- d - talo -oct-2-ulosonic acid (Ko), in which the axial hydrogen atom at the Kdo 3-position is replaced with OH. Here we report a unique Kdo 3-hydroxylase (KdoO) from Burkholderia ambifaria and Yersinia pestis , encoded by the bamb_0774 ( BakdoO ) and the y1812 ( YpkdoO ) genes, respectively. When expressed in heptosyl transferase-deficient Escherichia coli , these genes result in conversion of the outer Kdo unit of Kdo 2 -lipid A to Ko in an O 2 -dependent manner. KdoO contains the putative iron-binding motif, HXDX n >40 H. Reconstitution of KdoO activity in vitro with Kdo 2 -lipid A as the substrate required addition of Fe 2+ , α-ketoglutarate, and ascorbic acid, confirming that KdoO is a Fe 2+ /α-ketoglutarate/O 2 -dependent dioxygenase. Conversion of Kdo to Ko in Kdo 2 -lipid A conferred reduced susceptibility to mild acid hydrolysis. Although two enzymes that catalyze Fe 2+ /α-ketoglutarate/O 2 -dependent hydroxylation of deoxyuridine in fungal extracts have been reported previously, kdoO is the first example of a gene encoding a deoxy-sugar hydroxylase. Homologues of KdoO are found exclusively in Gram-negative bacteria, including the human pathogens Burkholderia mallei , Yersinia pestis , Klebsiella pneumoniae , Legionella longbeachae , and Coxiella burnetii , as well as the plant pathogen Ralstonia solanacearum .

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Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Dioxygenases in Burkholderia ambifaria and Yersinia pestis that hydroxylate the outer Kdo unit of lipopolysaccharide

Chung

Raetz

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…In Fig. 1A we present a proposed structure for the inner core region in B. cenocepacia, taking into account the high level of conservation of the inner core region in Burkholderia species (19,27,38). This region contains at least one residue of deoxy-manno-octulosonic acid, glycero-talo-octulosonic acid, and three glycero-manno-heptoses (Fig.…”

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confidence: 99%

A Complete Lipopolysaccharide Inner Core Oligosaccharide Is Required for Resistance of Burkholderia cenocepacia to Antimicrobial Peptides and Bacterial Survival In Vivo

Loutet¹,

Flannagan²,

et al. 2006

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Burkholderia cenocepacia is an important opportunistic pathogen of patients with cystic fibrosis. This bacterium is inherently resistant to a wide range of antimicrobial agents, including high concentrations of antimicrobial peptides. We hypothesized that the lipopolysaccharide (LPS) of B. cenocepacia is important for both virulence and resistance to antimicrobial peptides. We identified hldA and hldD genes in B. cenocepacia strain K56-2. These two genes encode enzymes involved in the modification of heptose sugars prior to their incorporation into the LPS core oligosaccharide. We constructed a mutant, SAL1, which was defective in expression of both hldA and hldD, and by performing complementation studies we confirmed that the functions encoded by both of these B. cenocepacia genes were needed for synthesis of a complete LPS core oligosaccharide. The LPS produced by SAL1 consisted of a short lipid A-core oligosaccharide and was devoid of O antigen. SAL1 was sensitive to the antimicrobial peptides polymyxin B, melittin, and human neutrophil peptide 1. In contrast, another B. cenocepacia mutant strain that produced complete lipid A-core oligosaccharide but lacked polymeric O antigen was not sensitive to polymyxin B or melittin. As determined by the rat agar bead model of lung infection, the SAL1 mutant had a survival defect in vivo since it could not be recovered from the lungs of infected rats 14 days postinfection. Together, these data show that the B. cenocepacia LPS inner core oligosaccharide is needed for in vitro resistance to three structurally unrelated antimicrobial peptides and for in vivo survival in a rat model of chronic lung infection.

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Chemistry and Biology of the Potent Endotoxin from a Burkholderia dolosa Clinical Isolate from a Cystic Fibrosis Patient

Lorenzo¹,

Sturiale

Palmigiano

et al. 2013

ChemBioChem

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This is the first report of the chemical and biological properties of the lipooligosaccharide (LOS) endotoxin isolated from Burkholderia dolosa IST4208, an isolate recovered from a cystic fibrosis (CF) patient in a Portuguese CF center. B. dolosa is a member of the Burkholderia cepacia complex, a group of closely related species that are highly problematic and opportunistic pathogens in CF. B. dolosa infection leads to accelerated loss of lung function and decreased survival. The structural determination of its endotoxin was achieved using a combination of chemistry and spectroscopy, and has revealed a novel endotoxin structure. The purified LOS was tested for its immunostimulatory activity on human HEK 293 cells expressing TLR-4, MD-2, and CD-14. In these assays, the LOS showed strong proinflammatory activity.

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Isolation and characterisation of disodium (4-amino-4-deoxy-β-l-arabinopyranosyl)-(1⃗8)-(d-glycero-α-d-talo-oct-2-ulopyranosylonate)-(2⃗4)-(methyl 3-deoxy-d-manno-oct-2-ulopyranosid)onate from the lipopolysaccharide of Burkholderia cepacia

Cited by 68 publications

References 22 publications

Dioxygenases in Burkholderia ambifaria and Yersinia pestis that hydroxylate the outer Kdo unit of lipopolysaccharide

Dioxygenases in Burkholderia ambifaria and Yersinia pestis that hydroxylate the outer Kdo unit of lipopolysaccharide

A Complete Lipopolysaccharide Inner Core Oligosaccharide Is Required for Resistance of Burkholderia cenocepacia to Antimicrobial Peptides and Bacterial Survival In Vivo

Chemistry and Biology of the Potent Endotoxin from a Burkholderia dolosa Clinical Isolate from a Cystic Fibrosis Patient

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