Effect of Cyclodextrins on the Biofilm Formation Capacity of Pseudomonas aeruginosa PAO1

Abstract

Quorum sensing (QS) is a population-density-dependent communication process of microorganisms to coordinate their activities by producing and detecting low-molecular-weight signal molecules. In pathogenic bacteria, the property controlled by QS is often related to infectivity, e.g., biofilm formation. Molecular encapsulation of the QS signals is an innovative method to prevent the signals binding to the receptors and to attenuate QS. Cyclodextrins (CDs) may form an inclusion complex with the signals, thus reducing the communication (quorum quenching, QQ). A systematic study was performed with α-, β-cyclodextrin, and their random methylated, quaternary amino and polymer derivatives to evaluate and compare their effects on the biofilm formation of Pseudomonas aeruginosa. To examine the concentration-, temperature- and time-dependency of the QQ effect, the CDs were applied at a 0.1–12.5 mM concentration range, and biofilm formation was studied after 6, 24, 48 and 72 h at 22 and 30 °C. According to the results, the QS mechanism was significantly inhibited; the size of the cavity, the structure of the substituents, as well as the monomeric or polymeric character together with the concentration of the CDs have been identified as key influencing factors of biofilm formation. Statistically determined effective concentration values demonstrated outstanding efficiency (higher than 80% inhibition) of α-CD and its random methylated and polymer derivatives both on the short and long term. In summary, the potential value of CDs as inhibitors of QS should be considered since the inhibition of biofilm formation could significantly impact human health and the environment.

Quorum quenching effect of cyclodextrins on the pyocyanin and pyoverdine production of Pseudomonas aeruginosa

“…Since our main goal in the case of testing pyocyanin production was the development of an environmentally friendly and reliable method, we only studied the effect of two native CDs (ACD and BCD molecules without any substitution of side alkyl chains) at 1, 5, and 10 mM concentration levels. GCD did not prove to be effective in previous investigations (Molnár et al 2021 ; Berkl et al 2022 ).…”

“…According to our previous studies (Berkl et al 2022 ), the autoinducer-dependent quorum sensing mechanism of biofilm formation in Pseudomonas aeruginosa model system was significantly inhibited by cyclodextrins. The quorum quenching effect (decreased biofilm formation capacity) of these cyclic oligosaccharides was clearly demonstrated.…”

“…The potential quorum quenching effect of α- and β-CD (ACD, BCD), randomly-methylated β-CD (RAMEB), quaternary ammonium α- and β-CD (QAACD, QABCD), (2-hydroxypropyl)-α- and β-CD (HPACD, HPBCD), sulfobutyl ether β-CD (SBEBCD), and α- and β-CD polymers (ACDPS, BCDPS) on the pyoverdine production of P. aeruginosa was tested at 0.5, 2.5, and 12.5 mM CD concentrations in a small-volume (200 μL) model system. The choice of these derivatives was based on our previous experience in the biofilm formation studies of P. aeruginosa PAO1 (Berkl et al 2022 ).…”

“…For the average molecular structure of the tested cyclodextrins please refer to Fig. 6 in Berkl et al ( 2022 ). To investigate concentration-dependent effects, the tested CD molecules were dissolved in sterile distilled water, and once complete dissolution was achieved, the stock solutions were adjusted to a concentration of 50 mM and subsequently sterile filtered through a 0.22-μm pore size filter.…”

“…Based on the result of their systematic study focusing on bioluminescence with 12 different cyclodextrins, the autoinducer-dependent quorum sensing mechanism was significantly inhibited by several tested CD compounds. Berkl et al ( 2022 ) were the first to demonstrate in a systematic study including 8 different CD derivatives, that CDs can attenuate biofilm formation, a QS-mediated virulence factor of P. aeruginosa PAO1. Their results revealed the ability of the α-CD, randomly methylated α- and β-CDs to significantly inhibit biofilm formation in P. aeruginosa suggesting their potential superiority in antibiofilm treatments when compared to conventional approaches like antibiotics.…”