title: A dose-response study of antibiotic resistance in Pseudomonas aeruginosa biofilms.
abstract: Bacterial biofilms show enormous levels of antibiotic resistance, but little is known about the underlying molecular mechanisms. Multidrug resistance pumps (MDRs) are responsible for the extrusion of chemically unrelated antimicrobials from the bacterial cell. Contribution of the MDR-mediated efflux to antibiotic resistance of Pseudomonas aeruginosa biofilms was examined by using strains overexpressing and lacking the MexAB-OprM pump. Resistance of P. aeruginosa biofilms to ofloxacin was dependent on the expression of MexAB-OprM but only in the low concentration range. Unexpectedly, biofilm resistance 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 responsible for very high resistance of P. aeruginosa biofilms to quinolones. Bacterial cells recovered from a biofilm and tested under nongrowing conditions with tobramycin exhibited higher resistance levels than planktonic cells but lower levels than cells of an intact biofilm.
authors.affiliation: Biotechnology Center, Tufts University, Medford, Massachusetts 02155, USA.
authors.forename: A
authors.initials: A
authors.lastname: Brooun
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: K
authors.initials: K
authors.lastname: Lewis
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002352:Carrier Proteins / Q000378:metabolism; D002939:Ciprofloxacin / Q000494:pharmacology; D015169:Colony Count, Microbial; D004352:Drug Resistance, Microbial; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D013753:Tetracycline Resistance
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa; D002939:Ciprofloxacin; D015242:Ofloxacin