Community Research and Development Information Service - CORDIS

FP7

INFIMAS Result In Brief

Project ID: 303088
Funded under: FP7-PEOPLE
Country: Switzerland

Novel antibiotic targets

The control of infectious diseases caused by adhesive bacteria represents a major medical challenge. European researchers proposed the exploitation of the bacterial adhesive structures as antibiotic targets.
Novel antibiotic targets
Bacteria contain on their surface elongated structures known as pili or fimbriae that help them attach onto target cells. These structures assemble by specific secretory machinery called the chaperone-usher pathway and are emerging as novel targets for the development of antibiotics.

Scientists on the EU-funded INFIMAS (The study of Initial limiting steps for fimbrae assembly in E.coli) study set out to dissect the pathway necessary for the development of fimbriae. As a study model, they used uropathogenic E.coli that attaches to urinary tract tissues and causes infections. They elucidated the steps and components responsible for triggering the polymerisation of Type 1 fimbriae.

Research activities focused on the outer membrane protein FimD that catalyses the polymerisation of fimbriae subunits on the surface of the bacteria. Scientists discovered that the first steps of fimbriae assembly involve changes of the FimD three-dimensional conformation to an active configuration by the protein subunit FimH. The association of FimD and FimH is driven by a sequence motif that scientists found to be conserved among different species. Work on FimD and FimH mutants led to the conclusion that the motif in both proteins is vital for fimbriae polymerisation.

The results of the INFIMAS project suggest that the sequence motif shared by FimD and its activator FimH is a key component for fimbriae formation. Partners are hopeful that this motif could serve as a new antibiotic target for the design of inhibitory peptides that could help overcome drug resistance.

Related information

Keywords

Antibiotic, fimbriae, E. coli, FimD, FimH, drug resistance
Record Number: 175117 / Last updated on: 2016-02-10
Domain: Biology, Medicine