Flagellin glycosylation with pseudaminic acid in Campylobacter and Helicobacter

prospects for development of novel therapeutics

Abu Iftiaf Md Salah Ud-Din, Anna Roujeinikova

Research output: Contribution to journalReview ArticleOtherpeer-review

4 Citations (Scopus)

Abstract

Many pathogenic bacteria require flagella-mediated motility to colonise and persist in their hosts. Helicobacter pylori and Campylobacter jejuni are flagellated epsilonproteobacteria associated with several human pathologies, including gastritis, acute diarrhea, gastric carcinoma and neurological disorders. In both species, glycosylation of flagellin with an unusual sugar pseudaminic acid (Pse) plays a crucial role in the biosynthesis of functional flagella, and thereby in bacterial motility and pathogenesis. Pse is found only in pathogenic bacteria. Its biosynthesis via six consecutive enzymatic steps has been extensively studied in H. pylori and C. jejuni. This review highlights the importance of flagella glycosylation and details structural insights into the enzymes in the Pse pathway obtained via a combination of biochemical, crystallographic, and mutagenesis studies of the enzyme–substrate and –inhibitor complexes. It is anticipated that understanding the underlying structural and molecular basis of the catalytic mechanisms of the Pse-synthesising enzymes will pave the way for the development of novel antimicrobials.

Original languageEnglish
Pages (from-to)1163-1178
Number of pages16
JournalCellular and Molecular Life Sciences
Volume75
Issue number7
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Bacterial flagellum
  • Bacterial motility
  • Bacterial virulence
  • Biosynthetic pathway
  • Crystal structure
  • O-linked glycosylation
  • Small molecule inhibitor

Cite this

@article{ac90fdf07ba8469a9e6b1bdea375b03c,
title = "Flagellin glycosylation with pseudaminic acid in Campylobacter and Helicobacter: prospects for development of novel therapeutics",
abstract = "Many pathogenic bacteria require flagella-mediated motility to colonise and persist in their hosts. Helicobacter pylori and Campylobacter jejuni are flagellated epsilonproteobacteria associated with several human pathologies, including gastritis, acute diarrhea, gastric carcinoma and neurological disorders. In both species, glycosylation of flagellin with an unusual sugar pseudaminic acid (Pse) plays a crucial role in the biosynthesis of functional flagella, and thereby in bacterial motility and pathogenesis. Pse is found only in pathogenic bacteria. Its biosynthesis via six consecutive enzymatic steps has been extensively studied in H. pylori and C. jejuni. This review highlights the importance of flagella glycosylation and details structural insights into the enzymes in the Pse pathway obtained via a combination of biochemical, crystallographic, and mutagenesis studies of the enzyme–substrate and –inhibitor complexes. It is anticipated that understanding the underlying structural and molecular basis of the catalytic mechanisms of the Pse-synthesising enzymes will pave the way for the development of novel antimicrobials.",
keywords = "Bacterial flagellum, Bacterial motility, Bacterial virulence, Biosynthetic pathway, Crystal structure, O-linked glycosylation, Small molecule inhibitor",
author = "{Salah Ud-Din}, {Abu Iftiaf Md} and Anna Roujeinikova",
year = "2018",
month = "4",
day = "1",
doi = "10.1007/s00018-017-2696-5",
language = "English",
volume = "75",
pages = "1163--1178",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Springer",
number = "7",

}

Flagellin glycosylation with pseudaminic acid in Campylobacter and Helicobacter : prospects for development of novel therapeutics. / Salah Ud-Din, Abu Iftiaf Md; Roujeinikova, Anna.

In: Cellular and Molecular Life Sciences, Vol. 75, No. 7, 01.04.2018, p. 1163-1178.

Research output: Contribution to journalReview ArticleOtherpeer-review

TY - JOUR

T1 - Flagellin glycosylation with pseudaminic acid in Campylobacter and Helicobacter

T2 - prospects for development of novel therapeutics

AU - Salah Ud-Din, Abu Iftiaf Md

AU - Roujeinikova, Anna

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Many pathogenic bacteria require flagella-mediated motility to colonise and persist in their hosts. Helicobacter pylori and Campylobacter jejuni are flagellated epsilonproteobacteria associated with several human pathologies, including gastritis, acute diarrhea, gastric carcinoma and neurological disorders. In both species, glycosylation of flagellin with an unusual sugar pseudaminic acid (Pse) plays a crucial role in the biosynthesis of functional flagella, and thereby in bacterial motility and pathogenesis. Pse is found only in pathogenic bacteria. Its biosynthesis via six consecutive enzymatic steps has been extensively studied in H. pylori and C. jejuni. This review highlights the importance of flagella glycosylation and details structural insights into the enzymes in the Pse pathway obtained via a combination of biochemical, crystallographic, and mutagenesis studies of the enzyme–substrate and –inhibitor complexes. It is anticipated that understanding the underlying structural and molecular basis of the catalytic mechanisms of the Pse-synthesising enzymes will pave the way for the development of novel antimicrobials.

AB - Many pathogenic bacteria require flagella-mediated motility to colonise and persist in their hosts. Helicobacter pylori and Campylobacter jejuni are flagellated epsilonproteobacteria associated with several human pathologies, including gastritis, acute diarrhea, gastric carcinoma and neurological disorders. In both species, glycosylation of flagellin with an unusual sugar pseudaminic acid (Pse) plays a crucial role in the biosynthesis of functional flagella, and thereby in bacterial motility and pathogenesis. Pse is found only in pathogenic bacteria. Its biosynthesis via six consecutive enzymatic steps has been extensively studied in H. pylori and C. jejuni. This review highlights the importance of flagella glycosylation and details structural insights into the enzymes in the Pse pathway obtained via a combination of biochemical, crystallographic, and mutagenesis studies of the enzyme–substrate and –inhibitor complexes. It is anticipated that understanding the underlying structural and molecular basis of the catalytic mechanisms of the Pse-synthesising enzymes will pave the way for the development of novel antimicrobials.

KW - Bacterial flagellum

KW - Bacterial motility

KW - Bacterial virulence

KW - Biosynthetic pathway

KW - Crystal structure

KW - O-linked glycosylation

KW - Small molecule inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85032509109&partnerID=8YFLogxK

U2 - 10.1007/s00018-017-2696-5

DO - 10.1007/s00018-017-2696-5

M3 - Review Article

VL - 75

SP - 1163

EP - 1178

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 7

ER -