Antibiotics as signalling molecules

Abstract

We present the argument that the majority of low-molecular-weight organic compounds made and secreted by microbes play roles as cell-signalling molecules in the environment. Of the large number of compounds isolated to date, only a small fraction have been shown to possess useful therapeutic antibiotic activity. However, most microbial metabolites modulate gene transcription at low concentrations, and this is proposed to be the primary effect of the compounds in the maintenance of microbial communities in the environment. Thus, microbial metabolites constitute a large collection of cell-signalling molecules that regulate gene expression in microbial populations and possibly the interactions of these populations with the surrounding organisms.

Figure 1

The nature and extent of transcription responses to bioactive small molecules are dependent on concentration. The low concentration effects are considered to be environmentally relevant.

Figure 2

Promoter expression induced by small molecules. LB agar plates with soft agar (0.7% agar) overlays containing 1 : 60 diluted overnight cultures of Salmonella typhimurium lux reporter plasmids, where the luxABCDE operon is fused to (a, b) the fadB and (c, d) the tsr genes, respectively. Filter discs containing the following compounds have been placed on top of the overlay: microcin J25, indolicidin, pleurocidin and CP26 (starting upper left and continuing clockwise). Figures (b, d) show light produced from reporter strains converted to the colour scale shown on the far right. The presence of a dark circle around the disc in two dimension containing pleurocidin (see arrow) indicates downregulation of transcription by the compound, as there is no visible growth inhibition in figure (c). The fadB and the tsr promoters were selected for their general response to various antibiotics and are two promoters used in antibiotic identification panels.