Mechanisms of antibiotic resistance in Pseudomonas aeruginosa biofilms

Pseudomonas aeruginosa is a major cause of life-threatening acute infections and life-long lasting chronic in-fections. The characteristic biofilm mode of life in P. aeruginosa chronic infections severely limits the efficacy of antimicrobial therapies, as it leads to intrinsic tolerance, involving physical and physiological factors in addition to biofilm-specific genes that can confer a transient protection against antibiotics promoting the development of resistance. Indeed, a striking feature of this pathogen is the extraordinary capacity to develop resistance to nearly all available antibiotics through the selection of chromosomal mutations, evidenced by its outstanding and versatile mutational resistome. This threat is dramatically amplified in chronic infections, driven by the frequent emergence of mutator variants with enhanced spontaneous mutation rates. Thus, this mini review is focused on describing the complex interplay of antibiotic resistance mechanisms in P. aeruginosa biofilms, to provide potentially useful information for the design of effective therapeutic strategies.