Hybrid Genome and Clinical Impact of Emerging Extensively Drug-Resistant Priority Bacterial Pathogen Acinetobacter baumannii in Saudi Arabia.

Acinetobacter baumannii is listed by the World Health Organization as an emerging bacterial priority pathogen, the prevalence and multidrug resistance of which have been increasing. This functional genomics study aimed to understand the drug-resistance mechanisms of an extensively drug-resistant (XDR) A. baumannii strain (IRMCBCU95U) isolated from a transtracheal aspirate sample from a female patient with end-stage renal disease in Saudi Arabia. The whole genome of IRMCBCU95U (4.3 Mbp) was sequenced using Oxford Nanopore long-read sequencing to identify and compare the antibiotic-resistance profile and genomic features of A. baumannii IRMCBCU95U. The antibiogram of A. baumannii IRMCBCU95U revealed resistance to multiple antibiotics, including cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem and piperacillin/tazobactam. A comparative genomic analysis between IRMCBCU95U and A. baumannii K09-14 and ATCC 19606 identified significant genetic heterogeneity and mosaicism among the strains. This analysis also demonstrated the hybrid nature of the genome of IRMCBCU95U and indicates that horizontal gene transfer may have occurred between these strains. The IRMCBCU95U genome has a diverse range of genes associated with antimicrobial resistance and mobile genetic elements (ISAba1 and IS26) associated with the spread of multidrug resistance. The presence of virulence-associated genes that are linked to iron acquisition, motility and transcriptional regulation confirmed that IRMCBCU95U is a priority human pathogen. The plasmid fragment IncFIB(pNDM-Mar) observed in the strain is homologous to the plasmid in Klebsiella pneumoniae (439 bp; similarity: 99.09%), which supports its antimicrobial resistance. From these observations, it can be concluded that the clinical A. baumannii IRMCBCU95U isolate is an emerging extensively drug-resistant human pathogen with a novel combination of resistance genes and a plasmid fragment. The complex resistome of IRMCBCU95U highlights the urgent need for genomic surveillance in hospital settings in Saudi Arabia to fight against the spread of extensively drug-resistant A. baumannii.