Fig. 4.

Mechanisms of antimicrobial resistance in P. aeruginosa. Mechanisms of antimicrobial resistance in P. aeruginosa can be divided into intrinsic antibiotic resistance (① outer membrane permeability, ② efflux systems, and ④antibiotic-modifying enzymes or ⑤ antibiotic-inactivating enzymes), acquired antibiotic resistance (⑥ resistance by mutations and acquisition of resistance genes), and adaptive antibiotic resistance (③ biofilm-mediated resistance). Alteration of outer membrane protein porins decreases the penetration of drugs into cells by reducing membrane permeability. The efflux system directly pumps out drugs. Drug-hydrolyzing and modification enzymes render them inactive. Similarly, some enzymes cause target alterations so that the drug cannot bind its target, resulting in drug inactivity. Antibiotic resistance genes carried on plasmids can be acquired via horizontal gene transfer from the same or different bacterial species,²²⁵ quorum-sensing signaling molecules activate the formation of biofilms, which act as physical barriers and prevent antibiotics penetrating the cell