Contributions of plasmid p1AB5075-encoded antibiotic resistance genes to multidrug resistance of Acinetobacter baumannii AB5075

Infections caused by multidrug-resistant Acinetobacter baumannii are considered a threat to human and animal health. The widely studied A. baumannii strain AB5075 displays a high degree of antibiotic resistance. In this study, we experimentally validated that antibiotic resistance is largely mediated by resistance genes located on plasmid p1AB5075. We used a p1AB5075-deficient AB5075 strain to assess individual contributions of p1AB5075-encoded antibiotic resistance genes by ectopically (over-)expressing each gene in the Δp1AB5075 background. By determining individual contributions of seven p1AB5075-encoded antibiotic resistance genes, we show individual and overlapping roles of genes for aminoglycoside resistance and uncover the importance of extended-spectrum β -lactamase bla GES-11 for monobactam and cephalosporin resistance in A. baumannii AB5075. We discovered that aminoglycoside N -acetyltransferase aaC(6′)-Ib3 ( aacA4 ), which was previously shown to confer resistance to tobramycin, provides broad resistance to gentamicin, kanamycin, amikacin, streptomycin and tobramycin when overexpressed in A. baumannii AB5075. Because p1AB5075 is transferable to a wide range of environmental and clinical A. baumannii strains and non- baumannii Acinetobacter species, the relevance of our findings extends beyond A. baumannii AB5075.