Modulation of P. aeruginosa quorum sensing and host immune response with biomimetic cyclodextrin enzyme models

Abstract

Scientists working in the field of biomimetic nanomaterials are usually inspired by evolutionary strategies. Bacteria evaluate their own population density and disease causing processes through a unique chemical communication. Language used for this communication, quorum sensing (QS), has been determined to be N-acyl-homoserine lactones (AHLs) for most of the bacteria. AHL hydrolysis by the lactonase enzymes (cysteine hydrolases or metalloenzymes) of host species is known to inhibit QS. Here, we present the first biomimetic quorum quenching approach with the use of supramolecular enzyme mimetics. Thiol bearing (CD-SH) and metal chelated (CD–Cu(II)) cyclodextrin derivatives are shown to modulate bacterial quorum sensing, and CD-SH interferes with the inflammatory immune response of P. aeruginosa-infected host human lung cells. Like natural defensive enzymes against bacteria, CD-based enzyme mimetics with a hydrophobic binding pocket reduce pyocyanin production in P. aeruginosa, modulate QS, and reduce biofilm formation. The viability of infected lung cancer cells is significantly restored, and mucin and interleukin expressions are reduced upon treatment with CD-SH. Considering the role of cytokines and mucin glycoproteins in cystic fibrosis pathogenesis, bacterial attachment and accumulation, the host immune modulatory effect of artificial enzyme mimetics can pave the way for the development of potential new treatment modality for patients suffering from CF.