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Preacinetobactin not acinetobactin is essential for iron uptake by the BauA transporter of the pathogen Acinetobacter baumannii

DOI: 10.7554/eLife.42270 DOI Help

Authors: Lucile Moynie (Wellcome Trust Centre of Human Genomics) , Ilaria Serra (University of Cagliari) , Mariano A. Scorciapino (University of Cagliari) , Emilia Oueis (The University of St Andrews) , Malcolm G. P. Page (The University of St Andrews) , Matteo Ceccarelli (University of Cagliari) , James Naismith (Wellcome Trust Centre of Human Genomics)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 7

State: Published (Approved)
Published: December 2018

Open Access Open Access

Abstract: New strategies are urgently required to develop antibiotics. The siderophore uptake system has attracted considerable attention but rational design of siderophore antibiotic conjugates requires knowledge of recognition by the cognate outer membrane transporter. Acinetobacter baumannii is a serious pathogen, which utilizes (pre)acinetobactin to scavenge iron from the host. We report the structure of the (pre)acinetobactin transporter BauA bound to the siderophore, identifying the structural determinants of recognition. Detailed biophysical analysis confirms that BauA recognises preacinetobactin. We show that acinetobactin is not recognised by the protein thus preacinetobactin is essential for iron uptake. The structure shows and NMR confirms that under physiological conditions a molecule of acinetobactin will bind to two free coordination sites on the iron preacinetobactin complex. The ability to recognise a heterotrimeric iron preacinetobactin acinetobactin complex may rationalize contradictory reports in the literature. These results open new avenues for the design of novel antibiotic conjugates (trojan horse) antibiotics.

Journal Keywords: Preacinetobactin; acinetobactin; siderophore-iron uptake system; BauA

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography