Screening for cholera biofilm inhibitors

Candidates—Kelly Peach, Nicholas Shikuma, and Walter Bray, UC Santa Cruz

Nominated by Roger Linington, UC Santa Cruz

The Deloitte QB3 Award for Innovation recognizes a graduate student, postdoc, staff scientist, or team from UC Berkeley, UC Santa Cruz, or UCSF who has made an advance with the capacity to improve human health. Candidates for were nominated by QB3 faculty. Finalists were chosen by a panel of expert judges.

We asked each nominee (or team) to answer a series of short questions, to give a snapshot of their project. Read their answers below. Leave a comment below to let us know what you think!

Walter, Kelly, and Nick of the Santa Cruz biofilm team.

Please describe your innovation.
We developed the first reported high-throughput, epifluorescent screen for identification of compounds that inhibit biofilm formation in Vibrio cholerae. Although biofilms are responsible for a 10-1000 fold increase in antibiotic resistance and mediate 60% of all human bacterial infections there are no commercially available therapeutics. Current methods used to screen chemical libraries are limited by indirect detection of inhibitor action and low-throughput formats. Our approach enables image-based identification of hits and distinguishes them as either antibiotics or biofilm inhibitors in a single screening event. Our system does not require specialized equipment, and screening can be completed in a single day.

Within the 140-character Twitter limit:

What’s the impact?
Antibiotic resistant biofilms mediate 60% of bacterial infections. There are no commercially available drugs; our screen will identify potential drugs. #winning

What’s the novelty?
The first high-throughput, image-based assay for biofilm inhibitors in V. cholerae. Performed in 1 day to rapidly classify compounds as antibiotics or inhibitors

What’s the utility?
This screen streamlines inhibitor identification and will provide compounds for use as coatings for medical implants or as components of antibiotic cocktails

Cholera bacteria can form a biofilm (left) that enhances their survival. Drug compounds that disrupt biofilm formation (right) will reduce virulence.

How does your research topic represent a strong advance in human health? And how will it influence the way we operate in science in the future?
Preventing biofilm formation will eliminate biofilm-mediated resistance to host immune responses and traditional antibacterial treatments. Considering biofilms contribute significantly to the pathogenicity of Vibrio cholerae, removing the capacity to form biofilms will reduce virulence. Epifluorescence microscopy coupled with new bioinformatic tools allows identification of subtle biofilm-related phenotypes at the primary screening stage. Streamlining the discovery process will move compounds to the development phase more quickly. Biofilm inhibitors will afford the development of coatings for medical devices burdened by biofilm colonization and usher in the use of sophisticated antibacterial cocktails containing antibiotics and biofilm inhibitors.

Reference:
An image-based 384-well high-throughput screening method for the discovery of biofilm inhibitors in Vibrio cholerae
Kelly C. Peach, Walter M. Bray, Nicholas J. Shikuma, Nadine C. Gassner, R. Scott Lokey, Fitnat H. Yildiz and Roger G. Linington
Mol. BioSyst., 2011, 7, 1176–1184