Discovery of small-molecule inhibitors of multidrug-resistance plasmid maintenance using a high-throughput screening approach.

ABSTRACT: Carbapenem-resistant Enterobacteriaceae (CRE) are multidrug-resistant pathogens for which new treatments are desperately needed. Carbapenemases and other types of antibiotic resistance genes are carried almost exclusively on large, low-copy-number plasmids (pCRE). Accordingly, small molecules that efficiently evict pCRE plasmids should restore much-needed treatment options. We therefore designed a high-throughput screen to identify such compounds. A synthetic plasmid was constructed containing the plasmid replication machinery from a representative Escherichia coli CRE isolate as well as a fluorescent reporter gene to easily monitor plasmid maintenance. The synthetic plasmid was then introduced into an E. coli K12 tolC host. We used this screening strain to test a libr

SUBMITTER: Zulauf KE 

PROVIDER: S-EPMC7703651 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature