Fluorescent optotracers for bacterial and biofilm detection and diagnostics

Abstract

Effective treatment of bacterial infections requires methods that accurately and quickly identify which antibiotic should be prescribed. This review describes recent research on the development of optotracing methodologies for bacterial and biofilm detection and diagnostics. Optotracers are small, chemically well-defined, anionic fluorescent tracer molecules that detect peptide- and carbohydrate-based biopolymers. This class of organic molecules (luminescent conjugated oligothiophenes) show unique electronic, electrochemical and optical properties originating from the conjugated structure of the compounds. The photophysical properties are further improved as donor-acceptor-donor (D-A-D)-type motifs are incorporated in the conjugated backbone. Optotracers bind their biopolymeric target molecules via electrostatic interactions. Binding alters the optical properties of these tracer molecules, shown as altered absorption and emission spectra, as well as ON-like switch of fluorescence. As the optotracer provides a defined spectral signature for each binding partner, a fingerprint is generated that can be used for identification of the target biopolymer. Alongside their use for in situ experimentation, optotracers have demonstrated excellent use in studies of a number of clinically relevant microbial pathogens. These methods will find widespread use across a variety of communities engaged in reducing the effect of antibiotic resistance. This includes basic researchers studying molecular resistance mechanisms, academia and pharma developing new antimicrobials targeting biofilm infections and tests to diagnose biofilm infections, as well as those developing antibiotic susceptibility tests for biofilm infections (biofilm-AST). By iterating between the microbial world and that of plants, development of the optotracing technology has become a prime example of successful cross-feeding across the boundaries of disciplines. As optotracers offers a capacity to redefine the way we work with polysaccharides in the microbial world as well as with plant biomass, the technology is providing novel outputs desperately needed for global impact of the threat of antimicrobial resistance as well as our strive for a circular bioeconomy.

Keywords: AST; Carbotrace; EbbaBiolight; Microbes; amyloid; antimicrobial susceptibility testing; cellulose; fungi; optotracing; polysaccharides.