## 6 Multidrug Resistance of _A. baumannii_
### Genetic Elements Responsible for A. baumannii Multidrug Resistance  
Members of the genus _Acinetobacter_ quickly develop resistance to antimicrobial compounds. Antibiotic resistance genes can be disseminated through various mechanisms of horizontal gene transfer such as transformation, conjugation, and transduction. _A. baumanniii_ appears to use all the mechanisms; however, recent studies point to natural transformation as the mechanism playing an important role in the acquisition of the multidrug resistance phenotype [196]. In this process, bacteria appeared to be capable of uptake, integration, and functional expression of naked fragments of extracellular DNA from the environment. Bacteria could use transformation to avoid being targeted by antibiotics by accepting the genetic variation present in their neighborhood, including drug resistance genes [197]. Multidrug resistance of _A. baumanniii_ is mainly due to the horizontal acquisition of resistance genes, although recent studies showed that increased expression of chromosomal genes for the efflux system plays a major role in MDR [177]. Often, _A. baumanniii_ resistance to more than one class of antibiotics occurs when genes encoding resistance to antimicrobial agents are physically located in close proximity to each other on mobile genetic elements such as plasmids, transposons, and integrons. Plasmid profiling revealed the presence of multiple plasmids of varying molecular sizes in more than 80% of _Acinetobacter_ isolates [198]. They constitute a reservoir of genes important not only for the dissemination of antibiotic resistance but also essential for bacteria adaptation and evolution. Recent analysis of 173 complete plasmid sequences from _A. baumanniii_ isolates originated from 17 countries revealed that 34.6% of the plasmids pose antibiotic resistance genes [199]. [PERSON] et al. constructed a classification system for the _A. baumannii_ plasmids based on the sequence of replicase genes, and they identified 19 homology groups (GR1-GR19) [200]. Fourteen additional groups of plasmids were recently proposed [199; 201; 202]. GR6 was the most prevalent group detected in antibiotic-resistant _A. baumannii_ isolates from Europe [203]. The GR6 plasmids harbor class D \(\beta\)-lactamase genes, including _bla\({}_{\text{OXA-23}}\)_, _bla\({}_{\text{OXA-58}}\)_, and _bla\({}_{\text{OXA-40}}\)_-aminoglycoso-resistant genes (_aph_(3')-Via, _andB, audA2, strA, strB, aacA4, aph_(3')-Via), and sulfonamide (_sul2_) and streptomycin (_strAB_) resistance genes [199; 200; 203]. IS and transposons (Tn) are able to move from one genomic location to another in the chromosome or plasmid DNA within a single cell [204]. IS may include a strong promoter that initiates the expression of a downstream gene, e.g., IS_Aba1_ located upstream of _bla\({}_{\text{OXA-51}}\)_ genes or the _adeABC_ operon leading to intrinsic _A. baumannii_ carbapenem resistance or multidrug resistance, respectively [194; 205]. A diverse range of composite Tn, which harbor antibiotic resistance genes flanked by IS, was identified in _A. baumannii_ isolates. These transposons encode AmpC cephalosporironases, OXA carbapenemases,aminoglycosidases, and NDM or VIM metallo-carbapenemases [179; 186; 206; 207; 208; 209; 210]. For example, a chromosomally located Tn125-like transposon containing the _bla_NDM-1 gene was identified in NDM-1-producing _A. baumannii_ from European countries [179]. The _bla_OXA-23 genes with adjacent IS_aba1_ were detected in globally disseminated transposons Tn2006 and Tn2008, as well as in Tn2009 from _A. baumannii_ strains isolated in China [206; 208]. The largest antibiotic resistance gene clusters in various _A. baumannii_ isolates are resistance islands designated AbaR1-R30. These complex transposons are located in the chromosomal _comM_ gene (encoding the ATP-ase), and they carry heavy-metal resistance determinants apart from antibiotic resistance genes [211; 125]. Most AbaRs from _A.