## 6 Multidrug Resistance of _A. baumannii_
### Genetic Elements Responsible for A. baumannii Multidrug Resistance
baumannii_ strains of international clone I share a backbone transposon Tn_6019_ interrupted by a large compound transposon that contains a variable-resistance region flanked by two copies of Tn_6018_[212]. AbaR1 contains genes conferring resistance to ampicillin (_veb1_ and _oxa10_), sulfonamides (three copies of the _sul1_ gene), streptomycin (two copies of _aadA1_; _strA_, _strB_), aminoglycosoxide (_aadB_, _aacC1_, _aphA1b_, _aacA_), chloramphenicol (_cmlA1_, _cmlA5_, _cmlA9_, and _catA1_), rifampin (_arr2_), trimethoprim (_dfrA1_ and _dfrA10_), and tetracycline (_tetA-A_ and _tetA-G_) [211]. Integrons are responsible for the dissemination of antibiotic resistance, especially among Gram-negative bacteria [213]. They can integrate into chromosomes or plasmid via site-specific recombination. These genetic elements are able to acquire, integrate, and express gene cassettes which can carry antibiotic resistance. Class 1 integrins are commonly found in _A. baumannii_ and typically encode genes for aminoglycoside resistance, Ambler class A \(\beta\)-lactamases, metallo-beta-lactamases, and oxacillinases, as well resistance to antiseptides and sulfonamides [196]. They were also reported in clinical _A. baumannii_ strains. Many reports showed that clinical _A. baumannii_ strains carrying integrons were significantly more resistant to all tested antibiotics than strains lacking integrons [214]. It should be noted that some mobile genetic elements and resistance genes are disseminated worldwide (e.g., IS_abal_, _bla_OXA-23, _bla_OXA-51), whereas others are distributed locally across different countries or regions (e.g., integrons and class B carbapenemases are more frequently found in Asia) [215; 216]. Cross-Resistance, Co-Regulatory Resistance, and Stress-Induced Resistance to Antibiotics in _A._ baumannii  
Antibiotics can induce selective pressure on bacterial populations, leading to antimicrobial resistance through a mechanism called cross-resistance. This mechanism confers resistance to an entire class of antibiotic and is mainly achieved via multidrug efflux pumps. In _A. baumannii_, efflux pumps can be specific for a single substrate or can confer resistance to multiple antimicrobials by facilitating the extrusion of a broad range of compounds including antibiotics, heavy metals, and biocides from the bacterial cell [177]. Other studies demonstrated that treatment of _A. baumannii_ infection with cationic microbial peptide colistin can induce not only increased resistance to antibiotics but also resistance to host cationic antimicrobials typically found at sites of inflammation. These findings showed that understanding the molecular basis of cross-resistance is important for the development of more effective therapeutic schemes [217]. Another mechanism involved in bacterial resistance is called co-regulatory resistance. This occurs when resistant genes to antimicrobial agents are controlled by regulatory proteins [218]. Commonality of target sites between different class of antibiotics leads to the selection of mutants and the emergence of cross-resistance, as well as the co-selection and persistence of antibiotic-resistant strains. The presence of class 1 integrins in _A. baumannii_ strains confers several phenotypes, including resistance, to a broad range of antibiotic classes, in addition to heavy metals and biocides [213]. In integrons, antibiotic resistance genes are under the control of a single promoter. As a result, these genes are expressed in a coordinated manner. Some microorganisms readily acquire antibiotic resistance mechanisms in response to environmental stresses. It was shown that different physiological conditions influenced antimicrobial susceptibility and porin expression in _A. baumannii_. For example, putative efflux transporters were induced by the physiological concentrations of NaCl, contributing to increased tolerance of _A. baumannii_ to aminoglycosides, carbapenems, quinolones, and colistin.