Acinetobacter baumannii has recently been identified by the World Health Organisation (WHO) as one of the top three groups of bacteria for which new antibiotics is needed urgently. A. baumannii is a hospital-acquired opportunistic pathogen, which is now considered a threat globally, mainly due to the persistent nature of this pathogen and its propensity to acquire antimicrobial resistance phenotypes at unforeseen rates.
The aim of this study was to use a recent multi-drug resistant isolate of A. baumannii to understand the complex cellular responses of this pathogen to several classes of antimicrobials. A panel of 20 antimicrobials were chosen, these included several classes of antibiotics; disinfectants and antiseptics. Changes in expression at both the protein and transcript levels in response to antimicrobial stress were studied using RNA-sequencing, mass spectrometry (SWATH-MS) and high-throughput phenotypic screening using a transposon mutant library.
While each antimicrobial stress showed a unique expression profile, clustering pattern of genes in response to the panel of antimicrobials revealed overlaps in gene expression, therefore suggesting similar mechanisms of antimicrobial resistance. For example, overlaps in expression were evident in several efflux pump genes, motility genes and iron acquisition systems. We further investigated the broad-spectrum antibiotic, Ciprofloxacin. The bactericidal action of Ciprofloxacin is well studied in other organisms, wherein it is known to inhibit enzymes including topoisomerases. The most highly upregulated genes in the Transcriptomics and Proteomics data for Ciprofloxacin stress were genes associated with the SOS response and phage genes. The next most highly up-regulated gene in Ciprofloxacin stress was a hypothetical protein of unknown function. Disruption of this hypothetical protein in A. baumannii renders it more susceptible to Ciprofloxacin. Additionally, orthologs of this hypothetical protein is conserved in the core genome of Acinetobacter and is encoded in the genome of a range of Proteobacterial species. Collectively, these preliminary data show a novel gene which confers resistance to the antibiotic Ciprofloxacin in Acinetobacter baumannii.