The nosocomial pathogen Acinetobacter baumannii utilises a number of virulence mechanisms enabling it to evade eradication and persist in the hospital environment. One mechanism A. baumannii employs to regulate the expression of virulence genes is via two component signal transduction systems (TCSTS). TCSTS are comprised of two proteins; a membrane-bound histidine kinase sensor and a cytosolic response regulator, linked via a phospho-relay system. It is recognised that in many A. baumannii isolates the adeRS TCSTS controls expression of the resistance nodulation division efflux pump adeABC. However, it is unknown if adeRS regulates additional genes important in virulence and cell survival. The aim of this work was to characterise the full potential of the adeR (A1S_1753) regulator and elucidate its transcriptome in the A. baumannii strain ATCC 17978.
An in-frame adeR deletion mutant of A. baumannii ATCC 17978 was generated by double homologous recombination. A multitude of in vitro assays were undertaken to phenotypically characterise the role of adeR. The ATCC 17978 parent and ∆adeR strains were also assessed transcriptomically, using RNA sequencing and the results validated by RT-PCR. RNA sequencing revealed that upon adeR deletion, the transcriptional levels of >180 genes were altered by 2-fold or greater. Of interest, iron sequestering systems including the acinetobactin biosynthesis/transport cluster, siderophore clusters and many genes involved in sulphur metabolism were down-regulated. Expression levels of multiple efflux pumps were affected, where in the absence of adeR, adeAB and the major facilitator superfamily pump craA were up-regulated. Surprisingly, phenotypic resistance profiles for ∆adeR only produced minor fold-changes to some of the antimicrobial compounds tested compared to wildtype. Through analysis of the ∆adeR transcriptome this study has identified that adeR not only regulates adeAB but also a number of genes important for iron homoeostasis and metabolic processes in A. baumannii ATCC 17978.