Screening a Commercial Library of Pharmacologically Active Small Molecules against Staphylococcus aureus Biofilms.

Autor:	Torres NS; Dental and Craniofacial Trauma Research and Tissue Regeneration, Institute of Surgical Research, JB Fort Sam Houston, Texas, USA Department of Biomedical Engineering, South Texas Center for Emerging Infectious Diseases, The University of Texas, San Antonio, Texas, USA., Abercrombie JJ; Dental and Craniofacial Trauma Research and Tissue Regeneration, Institute of Surgical Research, JB Fort Sam Houston, Texas, USA., Srinivasan A; Department of Biomedical Engineering, South Texas Center for Emerging Infectious Diseases, The University of Texas, San Antonio, Texas, USA Department of Biology, South Texas Center for Emerging Infectious Diseases, The University of Texas, San Antonio, Texas, USA., Lopez-Ribot JL; Department of Biology, South Texas Center for Emerging Infectious Diseases, The University of Texas, San Antonio, Texas, USA., Ramasubramanian AK; Department of Biomedical Engineering, South Texas Center for Emerging Infectious Diseases, The University of Texas, San Antonio, Texas, USA anand.ramasubramanian@utsa.edu kai.p.leung.civ@mail.mil., Leung KP; Dental and Craniofacial Trauma Research and Tissue Regeneration, Institute of Surgical Research, JB Fort Sam Houston, Texas, USA anand.ramasubramanian@utsa.edu kai.p.leung.civ@mail.mil.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2016 Sep 23; Vol. 60 (10), pp. 5663-72. Date of Electronic Publication: 2016 Sep 23 (Print Publication: 2016).
DOI:	10.1128/AAC.00377-16
Abstrakt:	It is now well established that bacterial infections are often associated with biofilm phenotypes that demonstrate increased resistance to common antimicrobials. Further, due to the collective attrition of new antibiotic development programs by the pharmaceutical industries, drug repurposing is an attractive alternative. In this work, we screened 1,280 existing commercially available drugs in the Prestwick Chemical Library, some with previously unknown antimicrobial activity, against Staphylococcus aureus, one of the commonly encountered causative pathogens of burn and wound infections. From the primary screen of the entire Prestwick Chemical Library at a fixed concentration of 10 μM, 104 drugs were found to be effective against planktonic S. aureus strains, and not surprisingly, these were mostly antimicrobials and antiseptics. The activity of 18 selected repurposing candidates, that is, drugs that show antimicrobial activity that are not already considered antimicrobials, observed in the primary screen was confirmed in dose-response experiments. Finally, a subset of nine of these drug candidates was tested against preformed biofilms of S. aureus We found that three of these drugs, niclosamide, carmofur, and auranofin, possessed antimicrobial activity against preformed biofilms, making them attractive candidates for repurposing as novel antibiofilm therapies. (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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