Complete 6-Deoxy-d-altro-heptose Biosynthesis Pathway from Campylobacter jejuni

McCallum, Matthew; Shaw, Steven D.; Shaw, Gary S.; Creuzenet, Carole

doi:10.1074/jbc.m112.390492

Cited by 23 publications

(82 citation statements)

References 53 publications

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“…The new Ddah* names assigned to the enzymes in this study were chosen to reflect the involvement of these enzymes in GDP-6-deoxy-D-altro-heptose synthesis (Tables 1 and 2) and are introduced to facilitate distinguishing them from other enzymes that are involved in 6-O-methyl-L-glucoheptose and are named Mlgh*. Although DdahB was anticipated to have C3/C5 epimerase activity based on sequence homologies to RmlC and RfbC, and DdahC was anticipated to have C3/C5 epimerase and C4 reductase activities similarly to GFS and GMER, we showed that DdahB only exerted its C3 epimerase activity and that DdahC only served as a reductase in the GDP-6-deoxy-D-altro-heptose synthesis pathway (25).…”

mentioning

confidence: 79%

“…Cloning of cj1427c, cj1428c, and cj1430c into the pET Vector and Protein Expression-The cj1427c, cj1428c, and cj1430c genes from C. jejuni strain NCTC 11168 coding for WcaG NCTC , MlghC, and MlghB, respectively, were PCR-amplified from genomic DNA using primers CJ1427 P2/P3, CJ1428 P2/P3, and CJ1430 P2/P3, respectively (Table 3), and cloned in the pET23 derivative (28) using standard procedures as done before for WcaG 81176 , DdahB, and DdahC from strain 81-176 (24,25). All constructs were sequenced at the Robarts Institute Sequencing Facility (London, Canada).…”

Section: Methodsmentioning

confidence: 99%

“…1A) (24,25). The new Ddah* names assigned to the enzymes in this study were chosen to reflect the involvement of these enzymes in GDP-6-deoxy-D-altro-heptose synthesis (Tables 1 and 2) and are introduced to facilitate distinguishing them from other enzymes that are involved in 6-O-methyl-L-glucoheptose and are named Mlgh*.…”

mentioning

confidence: 99%

“…Although D-altro heptose synthesis only involves C3 epimerization of the D-manno-heptose precursor followed by its reduction at C4 (25), the synthesis of L-gluco-heptose is anticipated to require epimerizations both on C3 and on C5 followed by reduction at C4 (Fig. 1B).…”

mentioning

confidence: 99%

“…1A). However, it affected the outcome of this pathway via modulation of DdahC activity (25). The role of WcaG NCTC on the L-gluco heptose synthesis pathway remains to be elucidated.…”

mentioning

confidence: 99%

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Comparison of Predicted Epimerases and Reductases of the Campylobacter jejuni d-altro- and l-gluco-Heptose Synthesis Pathways

McCallum¹,

Shaw

Creuzenet³

2013

Journal of Biological Chemistry

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Background: Modified heptoses are important for bacterial virulence. Results: We characterized novel L-gluco-heptose synthesis enzymes from Campylobacter jejuni and compared their specificity with D-altro-heptose synthesis enzymes. Conclusion: Significant differences of activities and specificities were observed despite high sequence similarities. Significance: The versatility of the enzymes can be exploited to synthesize novel carbohydrates for technological applications and to develop therapeutic inhibitors.

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mentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…1A). However, it affected the outcome of this pathway via modulation of DdahC activity (25). The role of WcaG NCTC on the L-gluco heptose synthesis pathway remains to be elucidated.…”

mentioning

confidence: 99%

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Comparison of Predicted Epimerases and Reductases of the Campylobacter jejuni d-altro- and l-gluco-Heptose Synthesis Pathways

McCallum¹,

Shaw

Creuzenet³

2013

Journal of Biological Chemistry

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Effect of the polysaccharide capsule and its heptose on the resistance of Campylobacter jejuni to innate immune defenses

Myles,

Barnawi,

Mahmoudpour

et al. 2024

MicrobiologyOpen

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Campylobacter jejuni is a commensal in many animals but causes diarrhea in humans. Its polysaccharide capsule contributes to host colonization and virulence in a strain‐ and model‐specific manner. We investigated if the capsule and its heptose are important for interactions of strain NCTC 11168 with various hosts and their innate immune defenses. We determined that they support bacterial survival in Drosophila melanogaster and enhance virulence in Galleria mellonella. We showed that the capsule had limited antiphagocytic activity in human and chicken macrophages, decreased adherence to chicken macrophages, and decreased intracellular survival in both macrophages. In contrast, the heptose increased uptake by chicken macrophages and supported adherence to human macrophages and survival within them. While the capsule triggered nitric oxide production in chicken macrophages, the heptose mitigated this and protected against nitrosative assault. Finally, the C. jejuni strain NCTC 11168 elicited strong cytokine production in both macrophages but quenched ROS production independently from capsule and heptose, and while the capsule and heptose did not protect against oxidative assault, they favored growth in biofilms under oxidative stress. This study shows that the wild‐type capsule with its heptose is optimized to resist innate defenses in strain NCTC 11168 often via antagonistic effects of the capsule and its heptose.

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Crystal structure of a GDP‐6‐OMe‐4‐keto‐L‐xylo‐heptose reductase from Campylobacter jejuni

2021

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Carbohydrates play a major role in infection strategies of various enteric pathogens. In Campylobacter jejuni, the most common cause of gastroenteritis, uniquely modified heptoses found in surface carbohydrates are synthesized by specific pathways. Owing to the importance of such pathways for the infectious potential of pathogens and/or their virulence, these biosynthesis pathways present potential targets for therapeutic intervention. Here, we determined the crystal structure of GDP‐6‐OMe‐4‐keto‐L‐xylo‐heptose reductase (MlghC), an enzyme within the L‐gluco‐heptose synthesis pathway of C. jejuni strain NCTC 11168. This enzyme lacks the canonical tyrosine residue of the conserved catalytic Ser‐Lys‐Tyr triad commonly found among functionally related reductases. Despite adopting the overall two‐domain fold shared with other short‐chain dehydrogenase/reductase family members, subtle structural differences in the interface between the cofactor‐ and substrate‐binding domains explain the absence of epimerase activity and different substrate specificity of this reductase. Modeling of the product‐bound complex based on the crystal structure presented here suggests that a tyrosine residue unique to MlghC replaces the missing canonical residue of the catalytic triad.

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Complete 6-Deoxy-d-altro-heptose Biosynthesis Pathway from Campylobacter jejuni

Cited by 23 publications

References 53 publications

Comparison of Predicted Epimerases and Reductases of the Campylobacter jejuni d-altro- and l-gluco-Heptose Synthesis Pathways

Comparison of Predicted Epimerases and Reductases of the Campylobacter jejuni d-altro- and l-gluco-Heptose Synthesis Pathways

Effect of the polysaccharide capsule and its heptose on the resistance of Campylobacter jejuni to innate immune defenses

Crystal structure of a GDP‐6‐OMe‐4‐keto‐L‐xylo‐heptose reductase from Campylobacter jejuni

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