Active efflux pumps serve as another mechanism of resistance, removing the antibiotic from its site of action before it can act. This is an important mechanism of β-lactam resistance in
P. aeruginosa, E. coli and Neisseria gonorrhoeae. Multidrug efflux pumps traverse both the inner and outer membranes of Gram-negative bacteria. The pumps are composed of a minimum of three proteins and are energized by the proton motive force and is produced by the respiratory enzymes and oxidative phosphorylation. Increased expression of these pumps is an important cause of antibiotic resistance. The onset of the mechanism of antibiotic resistance may represent a genetic occurrence [
12,
13,
14]. The mutation responsible for drug resistance is usually a modification at a specific site on bacterial chromosomes. The capture, accumulation and dissemination of resistance genes are largely due to the actions of mobile genetic elements (MGE), a term used to refer to elements that promote intracellular DNA mobility (e.g., from the chromosome to a plasmid or between plasmids) as well as those that enable intercellular DNA mobility [
15]. Thus, the resistance can be transferred from a resistant microorganism to a new location in the same or different DNA to a sensitive microorganism [
16]. Multidrug efflux pumps are incorporated into bacteria and their purpose is to transport antibiotics outside the outer membrane of bacteria. Moreover, drug-specific efflux mechanism is promoted by plasmids and others mobile transporters [
17]. All these components participate in specific activity promoting horizontal genetic exchange and contribute to achieve and disseminate the resistance genes. Bacteria efflux proteins are proteins identified primarily in Gram-negative bacteria but also exist in Gram-positive bacteria. They are divided into seven families. The seven families included in the resistance-nodulation-division (RND) superfamily are: the heavy metal efflux (HME), the nodulation factor export family (NFE), the major facilitator (MF) superfamily, the SecDF protein-secretion accessory protein family, the hydrophobe/amphiphile efflux-2 family, the eukaryotic sterol homeostasis family and the hydrophobe/amphiphile efflux-3 family. The efflux pumps of the RND superfamily, such as AcrB of
E. coli and MexB of
P. aeruginosa, play a fundamental role in promoting multidrug resistance. These pumps are associated with outer membrane channel such as TolC of
E. coli and OprM of
P. aeruginosa belonging to the OMF family proteins, the AcrA of
E. coli and MexA of
P. aeruginosa that are included into the MFP family. These three groups of proteins are essential for drug efflux and the mere lack of one these give the entire system a non-functional status. All these elements are involved in the intercellular mechanism of antibiotic resistance. Efflux mechanism or to be more precise, genes encoding efflux pumps are not commonly transmitted by mobile genetic elements. Only a few plasmid-mediated efflux pumps have been described in recent years. The transcription of genes involved in the efflux pumps is checked by local regulators. The overexpression of efflux genes, that are at the basis of Gram-negative bacteria resistance, is regulated by the mutation mechanism.