Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli

• DOI: 10.1128/mbio.02038-14
• Publication Date: 2014-10-29T01:49:03Z
• Authors: Sarah E. Greene; Jerome S. Pinkner; Erik Chorell; Karen W. Dodson; Carrie L. Shaffer; Matt S. Conover; Jonathan Livny; Maria Hadjifrangi...; Fredrik Almqvist; Scott J. Hultgren
• Keywords: Chaperone (clinical)

ABSTRACT Chaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show pilicide ec240 decreased the levels 1, P, S Transcriptomic proteomic analyses using cystitis isolate UTI89 revealed dysregulated motility. Paradoxically, transcript pilus genes increased during growth in ec240, even though level piliation decreased. In contrast, most downregulated transcripts after from genes. Type expression is controlled inversion fimS promoter element, which can oscillate between phase on off orientations. induced orientation, this effect was necessary for majority ec240’s inhibition transcriptional regulators SfaB PapB, induce orientation. Furthermore, motility abolished absence SfaB, SfaX, PapX regulators. contrast effects deletion operon led Thus, several uropathogenic Escherichia coli (UPEC) virulence factors through different mechanisms independent its biogenesis may have potential as an antivirulence compound. IMPORTANCE flagella play active roles pathogenesis a variety infections, including urinary tract infections mediated UPEC. These extremely common often recurrent increasingly caused antibiotic-resistant organisms. Preventing altered regulation assembly these important could aid development novel therapeutics. This study increases our understanding factors, providing new avenues target their expression.