Affiliation:
1. Department of Microbiology and Immunology, University of Rochester, Rochester, New York
2. Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado
Abstract
ABSTRACT
Pseudomonas aeruginosa
biofilms are extremely recalcitrant to antibiotic treatment. Treatment of cystic fibrosis patients with azithromycin (AZM) has shown promise. We used DNA microarrays to identify differentially expressed transcripts in developing
P. aeruginosa
biofilms exposed to 2 μg/ml AZM. We report that transcripts for multiple restriction-nodulation-cell division (RND) efflux pumps, known to be involved in planktonic antibiotic resistance, and transcripts involved in type III secretion were upregulated in the resistant biofilms that developed in the presence of AZM. Interestingly, the MexAB-OprM and MexCD-OprJ efflux pumps, but not type III secretion, appear to be integral to biofilm formation in the presence of AZM, as evidenced by the fact that a mutant deleted in both
mexAB-oprM
and
mexCD-oprJ
was unable to form a biofilm in the presence of AZM. A mutant deleted in type III secretion was still able to form biofilms in the presence of drug. Furthermore, single
mexAB-oprM
- and
mexCD-oprJ
-null mutants were able to form a biofilm in the presence of drug, indicating that either of the pumps can confer resistance to AZM during biofilm development. In contrast to planktonically grown cells, where no
mexC
expression was detectable regardless of the presence of AZM, biofilms exhibited induction of
mexC
expression from the outset of their formation, but only in the presence of AZM.
mexA
, which is constitutively expressed in planktonic cells, was uniformly expressed in biofilms regardless of the presence of AZM. These data indicate that the MexCD-OprJ pump acts as a biofilm-specific mechanism for AZM resistance.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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