| Title | High-throughput screens for small molecule inhibitors of Pseudomonas aeruginosa biofilm development. | | Author(s) | Junker LM, Clardy J | | Institution | Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115. | | Source | Antimicrob Agents Chemother 2007 Jul 30. | | Abstract | Pseudomonas aeruginosa is both a model biofilm forming organism and an opportunistic pathogen responsible for chronic lung infections in cystic fibrosis (CF) patients and infections in burn patients, among other maladies. Here we describe the development of an efficient high-throughput screen (HTS) to identify small molecule modulators of biofilm formation. This screen has been run on 66,095 compounds to identify those that prevent biofilm formation without affecting planktonic bacterial growth. The screen is a luminescence based attachment assay that has been validated for several strains of P. aeruginosa and compared to a well-established but low throughput crystal violet (CV) staining biofilm assay. P. aeruginosa strain PAO1 was selected for use in the screen both because it forms robust biofilms and has genetic information and tools available. The attachment inhibited mutant strain PAO1 DeltafliC was used as a screening positive control. We have also developed and validated a complementary biofilm detachment assay that can be used as an alternative primary screen or secondary screen for the attachment screening positive compounds. We have determined the potency of 61 compounds against biofilm attachment and have identified 30 compounds falling into different structure classes as biofilm attachment inhibitors with an EC50 of less than 20 microM. These small molecule inhibitors could lead to the identification of their biofilm relevant targets or potential therapeutics for P. aeruginosa infections. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 17664319 |
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