Abstract

ABSTRACTThe human pathogen Acinetobacter baumannii produces and utilizes acinetobactin for iron assimilation. Although two isomeric structures of acinetobactin, one featuring an oxazoline (Oxa) and the other with an isoxazolidinone (Isox) at the core, have been identified, their differential roles as virulence factors for successful infection have yet to be established. This study provides direct evidence that Oxa supplies iron more efficiently than Isox, primarily owing to its specific recognition by the cognate outer membrane receptor, BauA. The other components in the acinetobactin uptake machinery appear not to discriminate these isomers. Interestingly, Oxa was found to form a stable iron complex that is resistant to release of the chelated iron upon competition by Isox, despite their comparable apparent affinities to Fe(III). In addition, both Oxa and Isox were found to be competent iron chelators successfully scavenging iron from host metal sequestering proteins responsible for nutritional immunity. These observations collectively led us to propose a new model for acinetobactin-based iron assimilation at infection sites. Namely, Oxa is the principal siderophore mediating the core Fe(III) supply chain for A. baumannii, whereas Isox plays a minor role in the iron delivery and, alternatively, functions as an auxiliary iron collector that channels the iron pool toward Oxa. The unique siderophore utilization mechanism proposed here represents an intriguing strategy for pathogen adaptation under the various nutritional stresses encountered at infection sites.

Highlights

  • The human pathogen Acinetobacter baumannii produces and utilizes acinetobactin for iron assimilation

  • Analysis of the genomes of various clinical isolates showed the prevalence of genes associated with acinetobactin biosynthesis and utilization, suggesting that this process would be the major Fe(III) assimilation mechanism and that acinetobactin likely serves as an important virulence factor for this pathogen [23]

  • Sequence analysis of the corresponding gene products indicates that acinetobactin delivers iron intracellularly via a pathway commonly found in Gramnegative bacteria [29]

Read more

Summary

Introduction

The human pathogen Acinetobacter baumannii produces and utilizes acinetobactin for iron assimilation. Oxa was found to form a stable iron complex that is resistant to release of the chelated iron upon competition by Isox, despite their comparable apparent affinities to Fe(III) Both Oxa and Isox were found to be competent iron chelators successfully scavenging iron from host metal sequestering proteins responsible for nutritional immunity. These observations collectively led us to propose a new model for acinetobactin-based iron assimilation at infection sites. This study clearly identified the isomer containing an oxazoline core as the principal siderophore based on comparative analysis of the specificity of the acinetobactin uptake machinery, the stability of the corresponding iron complexes, and the iron scavenging activity against the host iron sequestering proteins. As detailed in our recent highlight article, the very significant progress made in the last decade has greatly enhanced our understanding of the physicochemical properties, iron-delivery function, and structure-function relationships of acinetobactin [24]

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call