Biofilm Detection and Control
Tomorrow’s antimicrobials and antibiotics must be effective against biofilm microbes, which are many-fold more resistant than planktonic cells. SCELSE’s biofilm detection and control programme identifies and develops compounds that target and interfere with key stages in biofilm development and maintenance. Biofilm-specific assays and a range of novel molecular-based systems are used to report on biofilm-unique targets and traits in populations and communities. The research involves computational and synthetic chemistry, transcriptomics and other specific and efficacy measures, as well as in vivo animal models.
Research projects
SCELSE’s biofilm detection and control integrated programme involves identifying compounds that specifically report on biofilms and the biofilm mode of life, together with developing anti-biofilm drugs to interfere with stages unique to and essential for biofilm development and maintenance. The rationale behind this effort is the now accepted realisation that tomorrow’s antimicrobials and antibiotics must be effective against biofilm microbes, which are many-fold more resistant than planktonic cells. SCELSE’s antibiofilm drugs programme identifies and develops compounds that interfere with key stages in biofilm development and maintenance. Biofilm-specific assays and a range of novel molecular-based systems are used to report on biofilm-unique targets and traits in populations and communities.
The antibiofilm drugs programme involves molecular design of reporter systems, computational and synthetic chemistry, transcriptomics and other specific and efficacy measures, and in vivo animal models.
This core program establishes and utilises unique biofilm traits in populations and communities and employs the molecular design of reporter systems, computational and synthetic chemistry, and transcriptomics, as well as and in vivo animal models for testing and validation.
More specifically, SCELSE’s research involves defining targets representing responses or structural features that are key for the biofilm biology. A range of reporter assays has been developed both virtually (in silico) and experimentally, targetting different regulatory levels of quorum sensing, c-di-GMP and nitric oxide intracellular signaling systems, matrix polymers, and secretory/export sites, all of which have delivered leads in library screens. Once identified, antibiofilm agents are tested in concert with antibiotics as tools to combat chronic infections. The programme also involves developing a sophisticated strategy for delivery of such drugs to target sites within the biofilm by creating double (or multiple) warhead compounds that release dispersal agents upon contact with a biofilm target, thus forcing the cells into a more susceptible planktonic state and improving antimicrobial/host immune system efficacy.
Topics include:
- Nitric oxide and its role in biofilm control
- Chemical biology approach for microbial control technologies
- Novel membrane-targeting antimicrobial agents
Structure of the RbdA protein. (a) Domain organisation of RbdA with boundaries given above the amino-acid sequence. Aminoacid catalytic motifs are indicated. (b) The cRbdA dimer from two perpendicular views, with each domain coloured and labelled. The PAS domain is coloured green, GGDEF in cyan, EAL brown, and connecting segments crucial for the protein dynamics (S- and H-helix) in magenta and labelled.
Conjugated oligoelectrolytes (membrane insertion molecules) that are shorter than the dimensions of the lipid bilayer disrupt the membrane when they insert themselves between the phospholipids, with potential antimicrobial activity.
