Chimeric Ligands of Pili and Lectin A Inhibit Tolerance, Persistence, and Virulence Factors of over a Wide Range of Phenotypes.

Bacteria readily form resilient phenotypes to counter environmental and antibiotic stresses. Here, we demonstrate a class of small molecules that inhibit a wide range of phenotypes and enable antibiotics to kill previously tolerant bacteria, preventing the transition of tolerant bacteria into a persistent population. We identified two proteins, type IV pili and lectin LecA, as receptors for our molecules by methods including a new label-free assay based on bacterial motility sensing the chemicals in the environment, the chemical inhibition of bacteriophage adsorption on pili appendages of bacteria, and fluorescence polarization.

Cell-Wall-Targeting Antibiotics Cause Lag-Phase Bacteria to Form Surface-Mediated Filaments Promoting the Formation of Biofilms and Aggregates.

Antibiotics are known to promote bacterial formation of enhanced biofilms, the mechanism of which is not well understood. Here, using biolayer interferometry, we have shown that bacterial cultures containing antibiotics that target cell walls cause biomass deposition on surfaces over time with a linear profile rather than the Langmuir-like profiles exhibited by bacterial adherence in the absence of antibiotics. We observed about three times the initial rate and 12 times the final biomass deposition on surfaces for cultures containing carbenicillin than without.