## 1 Introduction  
_P. aeruginosa_ is a significant cause of hospital-acquired infection [1]. Treatment of diseases brought about by _P. aeruginosa_ is complex due to its antibiotic resistance to multiple antimicrobial agents [2]. Infections caused by drug-resistant _P. aeruginosa_ lead to increased morbidity, death, extended duration in the hospital and cost of treatment [3]. Resistance can manifest from possessing resistance genes or changes that alter gene expression. In addition to the numerous known mechanisms of antibiotic resistance, overexpression of the efflux pump leads to decreased drug concentration, an essential means of antibiotic resistance. The efflux pump transporters are classified into the following superfamilies: the ATP-binding cassette (ABC) superfamily, the multidrug and toxic compound extrusion (MATE) superfamily, the major facilitator superfamily (MFS), the resistance nodulation and cell division (RND) superfamily, and the small multidrug resistance (SMR) superfamily. The extrusion of antibiotics through the multidrug efflux system of the RND superfamily is the most predominant mechanism in _P. aeruginosa_. The RND multidrug efflux systemshave three components: a cytoplasmic membrane, a periplasmic membrane fusion protein (MFP), and an outer membrane protein that helps to transport antibiotics from the cytoplasm via the periplasmic space to the outside of the cell [4]. The genetic makeup of _P. aeruginosa_ comprises many RND superfamilies' operons, such as _MexAB-OprM_, _MexCD-OprJ_, _MexEF-OprN_, _MexXY-OprM_, _MexK-OprM_, _MexGHI-OpmD_ and _MexVW-OprM_, which are responsible for intrinsic and acquired multidrug resistance. _MexAB-OprM_ was the first discovered out of all RND pumps to target multiple classes of antibiotics and common wild-type strains, hence its multidrug resistance. The substrates of _MexAB-OprM_ are chloramphenicol, \(\beta\)-lactams, carbapenem, fluoroquinolones, tetracyclines, trimethoprim and sulphonamides. Likewise, dyes, detergents, triclosan, and organic solvents are also substrates of MexAB-OprM [1]. _MexCD-OprJ_'s substrates include quinolones, tetracycline, chloramphenicol, acriflavine, ethidium bromide, triclosan and organic solvents [5]. The extrusion of aminoglycos is specific to MexXY-OprM [6]. Transcriptional repressors regulate efflux pump expression. These repressors block the transcription of operons. Intriguingly, the regulators are triggered by the substrates to be pumped out of the bacteria cell [7]. Repressor genes, such as MexR, NaID, and NaIC, downregulate _MexAB-OprM_ system expression [8]. The MexR gene, which encodes a repressor of the MarR family, is found upstream of the MexAB-OprM operon, forming a stable homodimer. Consequently, it downregulates transcription from the _MexAB-OprM_ operon when bound to an intergenic region [9]. NaIC and NaID belong to the TetR family; while the nalC is encoded by the NaIC protein, NaID, a transcriptional regulator, acts as a repressor of the _MexAB-OprM_ by attaching to a sequence between _MexAB-OprM_ and the MexR binding site near the MexA promoter. As a result, NaID deficiency in nalD-type mutants results in _MexAB-OprM_ overexpression [10]. The repressor genes of _MexCD-OprJ_ and _MexXY-OprM_ operons are _infxB and mexZ_, respectively, which obstructs the transcription of the operons. In addition, MexXY gene deletion results in _P. aeruginosa_'s susceptibility to aminoglycosoides, tetracycline, and erythromycincin [11]. The blockage of transcription of efflux pump operons by repressors confers multidrug resistance in _P. aeruginosa_ isolates. The efflux pump system's inner membrane component is the site for substrate attachment. However, a mutation in the DNA sequence of the inner membrane reduces its stability and, as a result, enables the RND multidrug efflux pumps [12]. Changes in the transmembrane domain of the inner membrane can impair the efflux pump [13; 14]. There are few reports on the burden of efflux pump genes of MDR _P.