Iron acquisition in Acinetobacter baumannii

Acinetobacter baumannii is a clinically important Gram-negative opportunistic nosocomial pathogen partly because of the advent of pan-drug resistant clinical isolates. This pathogen persists and grows under harsh conditions including iron limitation imposed by the environment and the human host. The ability of A. baumannii ATCC 19606^T to grow under iron-limiting conditions requires the production of the siderophore, acinetobactin, which was also demonstrated to be essential for this strain to cause a successful infection. Initial studies have examined components involved in synthesis and uptake of acinetobactin; however, other components of this siderophore-mediated system have yet to be identified or characterized. The acinetobactin chromosomal gene cluster harbors all the traits needed for biosynthesis, export, and transport of this siderophore with the exception of an entA ortholog, which is needed for the production of acinetobactin precursor, 2,3-dihydroxybenzoic acid. Accordingly, the entA ortholog in ATCC 19606^T was identified using genetic complementation and found located in a different genomic region next to genes coding for iron acquisition functions. Analysis of the nucleotide sequence of this ortholog with other A. baumannii sequenced genomes revealed that while most of the strains code for an active entA gene, the clinical isolate AYE has a natural entA mutation and does not produce acinetobactin. Despite not being able to produce acinetobactin, AYE is still able to grow under iron-limiting conditions, a phenotype that is in accordance with the fact that this strain produces an uncharacterized hydroxamate siderophore, which we called baumannoferrin. Comparison of the siderophore-mediated system between ATCC 19606^T and AYE underline the ability of different A. baumannii isolates to acquire iron using different systems. The ATCC 19606^T acinetobactin gene cluster also includes two genes coding for ABC-type efflux transport functions predicted to be involved in acinetobactin secretion. Accordingly, we demonstrated that A. baumannii requires BarA and BarB for efficient secretion of acinetobactin although additional transport systems could be involved in the secretion of this siderophore. Taken together, the results from this study furthered our understanding of the acinetobactin-mediated siderophore system while concurrently demonstrating the diversity of iron-acquisition functions this pathogen expresses to persist and cause infection under restricted conditions, such as those found in medical settings and the human host.