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

14 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

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