Pneumonia infection in mice reveals the involvement of the feoA gene in the pathogenesis of Acinetobacter baumannii

Abstract

Acinetobacter baumannii has emerged in the last decade as an important nosocomial pathogen. To identify genes involved in the course of a pneumonia infection, gene expression profiles were obtained from A. baumannii ATCC 17978 grown in mouse infected lungs and in culture medium. Gene expression analysis allowed us to determine a gene, the A1S_0242 gene (feoA), over-expressed during the pneumonia infection. In the present work, we evaluate the role of this gene, involved in iron uptake. The inactivation of the A1S_0242 gene resulted in an increase susceptibility to oxidative stress and a decrease in biofilm formation, in adherence to A549 cells and in fitness. In addition, infection of G. mellonella and pneumonia in mice showed that the virulence of the Δ0242 mutant was significantly attenuated. Data presented in this work indicated that the A1S_0242 gene from A. baumannii ATCC 17978 strain plays a role in fitness, adhesion, biofilm formation, growth, and, definitively, in virulence. Taken together, these observations show the implication of the feoA gene plays in the pathogenesis of A. baumannii and highlight its value as a potential therapeutic target.

The Crystal Structure of Klebsiella pneumoniae FeoA Reveals a Site For Protein-Protein Interactions

“…Our discovery of a site for FeoA-mediated proteinprotein interactions opens up several exciting avenues for future research on the Feo system. Numerous studies have demonstrated that FeoA is a virtually indispensable component of the bacterial Feo system, [24][25][26][27] likely due to FeoA's regulatory role in modulating ferrous iron import through its interaction with FeoB. Furthermore, the disruption of protein-protein interactions mediated by complex surface recognition sites along SH3-like domains like FeoA is an active area of pharmacological development in eukaryotes.…”

Implication of HisF fromAcinetobacter baumanniiin persistence during a pneumonia infection

“…First, an experimental model of pneumonia in mice was employed to describe the transcriptome of the A. baumannii ATCC 17978 strain during the course of the infection, as previously published (11). A bronchoalveolar lavage (BAL) was performed to obtain bacteria suitable for RNA extraction ( in vivo samples).…”

“…Raw data were deposited in the GEO database under the accession code GSE100552. Gene expression profiles were determined and analyzed as previously described (11). Transcriptomic analysis revealed that the A1S_3245 gene was over-expressed in bacteria isolated during the lung infection (7.2-fold change), compared with bacteria grown in vitro .…”

“…Thus, the isogenic deletion derivative strain Δ3245 was obtained from the A. baumannii ATCC 17978 strain by double crossover recombination using the suicide vector pMo130, as described previously (11, 12). The upstream and downstream regions flanking the A1S_3245 gene were PCR-amplified and cloned into the vector pMo130 using the primers shown in Table S1.…”

“…Phenotypes of the parental and the mutant Δ3245 strains were compared through several in vitro assays previously described (11, 13), these including determination of biofilm, attachment to A549 human alveolar epithelial cells and motility abilities, as well as analysis of fitness and antimicrobial susceptibility (by disk diffusion assays), and no significant differences were observed (data not shown). Also, survival rates of A549 alveolar epithelial cells infected with the ATCC 17978 and the mutant Δ3245 strains were analyzed finding no differences.…”