KEYWORDS: antibiotics´bioorganic chemistry´chaperone proteins´peptidomimetics The heavy use of antibiotics during the second half of the last century has resulted in widespread bacterial resistance. Overcoming resistance requires the development of antibiotics aimed at new targets in microorganisms. Preferably, such targets should be highly conserved in bacteria and required for pathogenesis, b...

Minimum requirements have been determined for synthesis and secretion of the Pediococcus antimicrobial peptide, pediocin AcH, in Escherichia coli. The functional mature domain of pediocin AcH (Lys+1 to Cys+44) is targeted into the E. coli sec machinery and secreted to the periplasm in active form when fused in frame to the COOH terminus of the secretory protein maltose-binding protein (MBP). Th...

The class of proteins collectively known as periplasmic immunoglobulin-like chaperones play an essential role in the assembly of a diverse set of adhesive organelles used by pathogenic strains of Gram-negative bacteria. Herein, we present a combination of genetic and structural data that sheds new light on chaperone-subunit and subunit-subunit interactions in the prototypical P pilus system, an...

P pili are important adhesive fibres involved in kidney infection by uropathogenic Escherichia coli strains. P pili are assembled by the conserved chaperone-usher pathway, which involves the PapD chaperone and the PapC usher. During pilus assembly, subunits are incorporated into the growing fiber via the donor-strand exchange (DSE) mechanism, whereby the chaperone's G1 beta-strand that compleme...

The binding of uropathogenic Escherichia coli is mediated at the tips of pili by the PapG adhesin, which recognizes the Galalpha(1-4)Gal disaccharide on the uroepithelial surface. These receptors have been identified unequivocally in the human and murine urinary tracts but not in intestinal epithelium, yet uropathogenic E. coli strains are commonly found in normal colonic microflora. The gastro...

A chemical synthesis platform with broad applications and flexibility was rationally designed to inhibit biogenesis of adhesive pili assembled by the chaperone-usher pathway in Gram-negative pathogens. The activity of a family of bicyclic 2-pyridones, termed pilicides, was evaluated in two different pilus biogenesis systems in uropathogenic Escherichia coli. Hemagglutination mediated by either ...

* The first author is supported by National Natural Science Foundation of China (No. 71471090, 11001052), the Humanities and Social Sciences Foundation of the Ministry of Education of China (No. 14YJCZH182), China Postdoctoral Science Foundation (No. 2014T70449, 2012M520964), Natural Science Foundation of Jiangsu Province of China (No. BK20131339), Qing Lan Project, PAPD, Project of Constructio...

Present: The current funding acknowledgment information is incorrect. Correct: The proper funding information appears below. The authors sincerely apologize for this oversight. FUNDING This work was supported by the National Natural Science Foundation Project of International Cooperation (NSFC-NIH, 81361120398); the National Natural Science Foundation of China (81272712, 81572362); the Priority...