Withdrawn 11th Annual Conference of the International Chemical Biology Society 2022

Benzimidazole derivatives with molecular self-assembly properties: An innovative approach for inducing fast and effective bacterial flocculation (#119)

Isalyne Drewek 1 2 , Aurélie Pietka 1 2 , Dimitri Stanicki 1 , Nathan Fraikin 3 , Laurence Van Melderen 3 , Mathieu Surin 4 , Philippe Leclère 5 , Ruddy Wattiez 2 , Sophie Laurent 1 6
  1. NMR and Molecular Imaging Laboratory, General, Organic and Biomedical Chemistry Unit, University of Mons, Mons, Belgium
  2. Proteomics and Microbiology Laboratory, University of Mons, Mons, Belgium
  3. Cellular and Molecular Microbiology Laboratory, University of Brussels, Gosselies, Belgium
  4. Chemistry of Novel Materials Laboratory, University of Mons, Mons, Belgium
  5. Physics of Nanomaterials and Energy Laboratory, University of Mons, Mons, Belgium
  6. Center for Microscopy and Molecular Imaging, University of Mons, Mons, Belgium

Bacterial flocculation is a biological phenomenon that has shown a growing interest in recent years due to its various applications, ranging from wastewater treatment to biodegradation or biocatalytic processes. During this phenomenon, bacteria form eye-visible flocs, thus allowing easy recovery of the cells. This process can be observed naturally but can also be enhanced using flocculating agents1. The mechanism of action of those agents is mainly based on electrostatic interactions between the bacterial membrane (negatively charged) and the flocculating agents (positively charged)2. However, this specific mechanism of action, combined with high cost and toxicity are constraints preventing the use of current flocculating agents on an industrial scale1.

As the benzimidazole moiety is found in many structures exhibiting interesting biological activity3, our work focused on the development of new heterocyclic derivatives bearing two benzimidazole units. In recent studies, we have highlighted that some of these structures exhibit an important activity against both Gram(+) and Gram(-) bacterial strains characterized by the rapid appearance (within a few minutes) of flocs when the bacterial suspension is incubated with a low concentration of derivative.

As the structure of our derivatives does not suggest a conventional flocculation mechanism (no positive charge carried by the molecule), we decided to carry out further studies. In first instance, various microbiological studies (microscopic studies, metabonomic experiments, biological characterizations of the flocs, …) enabled to highlight that the observed flocculation doesn’t result from a biological process, but rather from physicochemical ones. It is widely referenced in the literature that many heterocyclic structures can self-assemble in solution to form supramolecular arrangements4. By performing AFM studies, we were able to demonstrate the ability of our compounds to form fibre networks in solution following a molecular self-assembly process. As a result, we were able to correlate the formation of this network with the appearance of the flocculation phenomenon, this leading to the emergence of a new class of fast and efficient bacterial flocculating agents.

  1. Ojima, Y., Azuma, M. & Taya, M. Inducing flocculation of non-floc-forming Escherichia coli cells. World J Microbiol Biotechnol 34, 185 (2018).
  2. Yang, Z. et al. Flocculation of Escherichia coli Using a Quaternary Ammonium Salt Grafted Carboxymethyl Chitosan Flocculant. Environ. Sci. Technol. 48, 6867–6873 (2014).
  3. Prasad, P. M. K., S., A. K. & S., R. Potent Biological Agent Benzimidazole–a Review. Int J Pharm Pharm Sci 8, 22 (2016).
  4. Palermo, V. & Samorì, P. Molecular Self-Assembly across Multiple Length Scales. Angew. Chem. Int. Ed. 46, 4428–4432 (2007).