Using siclopps for the discovery of novel antimicrobial peptides and their targets.

High throughput screening of SICLOPPS libraries afforded six distinct cyclic peptides that inhibit Escherichia coli growth both in liquid and solid media. One of these peptides (LN05) reduced both bacterial growth rate and caused cell aggregation in liquid media. Mutant bacteria immune to LN05 action were obtained at a frequency of 10(-7). Over-expression of an E. coli genomic library in the presence of LN05 production resulted in enrichment of a single genomic construct, a fragment of the NarZ gene.