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

• Published in: eLife Vol. 7
• Main Authors: Moynié, Lucile, Serra, Ilaria, Scorciapino, Mariano A, Oueis, Emilia, Page, Malcolm Gp, Ceccarelli, Matteo, Naismith, James H
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 18-12-2018; eLife Sciences Publications, Ltd
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - metabolism; Antibiotics; Bacteria; Binding sites; Biochemistry and Chemical Biology; Crystallography, X-Ray; Gram-negative bacteria; Imidazoles - chemistry; Imidazoles - metabolism; Iron; Iron - metabolism; iron uptake; Ligands; Magnetic Resonance Spectroscopy; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - metabolism; NMR; Nosocomial infections; Nuclear magnetic resonance; Oxazoles - chemistry; Oxazoles - metabolism; Pathogens; Protein Binding; Protein Multimerization; Protein Precursors - chemistry; Protein Precursors - metabolism; siderophore; Structural Biology and Molecular Biophysics; Trace Elements - metabolism; Cagliari Italy; England; United States > US; Acinetobacter baumannii; chemical biology; biochemistry; iron uptake; structural biology; molecular biophysics; antibiotics; siderophore
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.42270

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.
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.