Biosynthesis of UDP--N-Acetyl-d-mannosaminuronic Acid and CMP--N-Acetyl-d-neuraminic Acid for the Capsular Polysaccharides of Campylobacter jejuni. Academic Article uri icon

abstract

  • Campylobacter jejuni is a human pathogen and a leading cause of food poisoning in North America and Europe. The exterior surface of the bacterial cell wall is attached to a polymeric coat of sugar molecules known as the capsular polysaccharide (CPS) that helps protect the organism from the host immune response. The CPS is composed of a repeating sequence of common and unusual sugar residues. In the HS:11 serotype of C. jejuni, we identified two enzymes in the gene cluster for CPS formation that are utilized for the biosynthesis of UDP--N-acetyl-d-mannosaminuronic acid (UDP-ManNAcA). In the first step, UDP--N-acetyl-d-glucosamine (UDP-GlcNAc) is epimerized at C2 to form UDP--N-acetyl-d-mannosamine (UDP-ManNAc). This product is then oxidized by a NAD+-dependent C6-dehydrogenase to form UDP-ManNAcA. In the HS:6 serotype (C. jejuni strain 81116), we identified three enzymes that are required for the biosynthesis of CMP--N-acetyl-d-neuraminic acid (CMP-Neu5Ac). In the first step, UDP-GlcNAc is epimerized at C2 and subsequently hydrolyzed to form N-acetyl-d-mannosamine (ManNAc) with the release of UDP. This product is then condensed with PEP by N-acetyl-d-neuraminate synthase to form N-acetyl-d-neuraminic acid (Neu5Ac). In the final step, CMP-N-acetyl-d-neuraminic acid synthase utilizes CTP to convert this product into CMP-Neu5Ac. A bioinformatic analysis of these five enzymes from C. jejuni serotypes HS:11 and HS:6 identified other bacterial species that can produce UDP-ManNAcA or CMP-Neu5Ac for CPS formation.

published proceedings

  • Biochemistry

altmetric score

  • 1.25

author list (cited authors)

  • Ghosh, M. K., & Raushel, F. M.

citation count

  • 0

complete list of authors

  • Ghosh, Manas K||Raushel, Frank M

publication date

  • February 2024