The impact of iron acquisition systems in Yersinia virulence.

• Applicant: Dr. Alexander Rakin
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 103626087

Iron supply is a prerequisite for successful survival and efficient dissemination of pathogenic bacteria. The pathogenic Yersinia possess several iron transport systems but only a single endogenous yersiniabactin siderophore (Ybt) biosynthetic system. However, not all highly-pathogenic yersiniae use yersiniabactin. Nearly half of Y. pseudotuberculosis O:3 strains do not possess Ybt but display siderophore activity. Using genomic subtractive hybridization we demonstrated that the yptb3290-yptb3298 cluster might be responsible for production of this siderophore designated as pseudochelin (Pch). To prove the impact of the pch genes in siderophore production we inactivated a potential siderophore biosynthetic gene yptb3297 in the siderophore-positive Y. pseudotuberculosis O:3. The constructed mutant demonstrated no iron binding activity however relatively low siderophore activity can still be detected after prolonged cultivation. This residual siderophore activity also detected in Y. pestis was designated as yersiniachelin (Ych). We propose that the ysu gene cluster (Yersinia siderophore uptake) is responsible for yersiniachelin production. To address the nature of these two uncharacterized siderophores and their role in Yersinia pathogenicity we are constructing a panel of mutants in individual siderophore systems and double mutants. The pseudochelin and yersiniachelin siderophores have been purified and characterized biochemically and their structures will be determined. The molecular mass of the heterocyclic pseudochelin is 406 Da, while hydroxamate yersiniachelin is 610 Da. We would like to address the role of pseudochelin and yersiniachelin siderophores in iron acquisition, pathogenicity and fitness as well as to elucidate their place in a hierarchy of iron acquisition systems in Yersinia.

• DFG Programme: Research Grants