A dose-response study of antibiotic resistance in Pseudomonas aeruginosa biofilms

Bacterial biofilms show enormous levels of antibiotic resistance, but littl e is known about the underlying molecular mechanisms. Multidrug resistance pumps (MDRs) are responsible for the extrusion of chemically unrelated anti microbials from the bacterial cell. Contribution of the MDR-mediated efflux to antibiotic resistance of Pseudomonas aeruginosa biofilms was examined b y using strains overexpressing and lacking the MexAB-OprM pump. Resistance of P, aeruginosa biofilms to ofloxacin was dependent on the expression of M exAB-OprM but only in the low concentration range, Unexpectedly, biofilm re sistance to ciprofloxacin, another substrate of MexAB-OprM, did not depend on the presence of this pump. Dose-dependent killing indicated the presence of a small "superresistant" cell fraction. This fraction was primarily res ponsible for very high resistance of P, aeruginosa biofilms to quinolones. Bacterial cells recovered front a biofilm and tested under nongrowing condi tions with tobramycin exhibited higher resistance levels than planktonic ce lls but lower levels than cells of an intact biofilm.