Molecular basis of azithromycin-resistant Pseudomonas aeruginosa biofilms

被引:133
作者
Gillis, RJ
White, KG
Choi, KH
Wagner, VE
Schweizer, HP
Iglewski, BH
机构
[1] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA
[2] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA
关键词
D O I
10.1128/AAC.49.9.3858-3867.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 mu g/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-opJ-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.
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收藏
页码:3858 / 3867
页数:10
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