Experimental evolution reveals adaptive pathways to reduced antibiotic susceptibility in Pseudomonas aeruginosa biofilms

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Abstract In the present study, we used an experimental evolution approach to investigate how reduced antibiotic susceptibility develops in biofilms formed bywhen they are exposed to the clinically relevant antibiotics tobramycin and meropenem. Two biofilm model systems were used, one mimicking surface-attached biofilms (multiple independentlineages originating fromAA2-1 and maintained for 4–10 cycles) and one mimicking biofilm aggregates in cystic fibrosis sputum (multiple independentlineages originating from 6 different reference strains and maintained for 15 cycles). Whole-genome sequencing of evolved populations revealed both known and previously unknown genetic adaptations that reduce antibiotic susceptibility. While reduced susceptibility to meropenem commonly arose from mutations in, we also identified a role for. The development of reduced susceptibility towards tobramycin was more complex, with mutations in,,,,andassociated with adaptation to this antibiotic. Our findings underscore the multifaceted strategies employed byto withstand antibiotic pressure in biofilms.