Abstract
Pseudomonas aeruginosa is an opportunistic pathogen using virulence factors and biofilm regulated by quorum sensing (QS) systems to infect patients and protect itself from environmental stress and antibiotics. Interfering with QS systems is a novel approach to combat P. aeruginosa infections without killing the bacteria, meaning that it is much harder for bacteria to develop drug resistance. A marine fungus Cladosporium sp. Z148 with anti-QS activity was obtained from Jiaozhou Bay, China. Cladodionen, a novel QS inhibitor, was isolated from the extracts of this fungus. Cladodionen had a better inhibitory effect than pyocyanin on the production of elastase and rhamnolipid. It also inhibited biofilm formation and motilities. The mRNA expressions of QS-related genes, including receptor proteins (lasR, rhlR and pqsR), autoinducer synthases (lasI, rhlI and pqsA) and virulence factors (lasB and rhlA) were down-regulated by cladodionen. Molecular docking analysis showed that cladodionen had better binding affinity to LasR and PqsR than natural ligands. Moreover, the binding affinity of cladodionen to LasR was higher than to PqsR. Cladodionen exhibits potential as a QS inhibitor against P. aeruginosa, and its structure–activity relationships should be further studied to illustrate the mode of action, optimize its structure and improve anti-QS activity.
Highlights
Pseudomonas aeruginosa is an opportunistic pathogen causing a wide range of acute and chronic infections in cystic fibrosis patients, immunocompromised individuals, burn victims and patients who are mechanically ventilated [1]
Its effect on elastase that the las and rhlCladodionen systems were more susceptible to cladodionen than the effect on elastase and rhamnolipid was more significant than on pyocyanin. These results indicated and rhamnolipid was more significant than on pyocyanin. These results indicated that the las and rhl that the las and rhl systems were more susceptible to cladodionen than the PQS system
The results of real-time RT-PCR confirmed that the las and rhl systems were more susceptible to cladodionen than the PQS system
Summary
Pseudomonas aeruginosa is an opportunistic pathogen causing a wide range of acute and chronic infections in cystic fibrosis patients, immunocompromised individuals, burn victims and patients who are mechanically ventilated [1]. Antibiotics cause enormous selective pressure by killing P. aeruginosa or inhibiting its growth, leading to the development of drug resistance in this bacterium. Virulence factors and multiple mechanisms, including the formation of a biofilm, are used by P. aeruginosa to infect hosts and protect itself from environmental stress and antibiotics [2]. The production of virulence factors and the formation of biofilms are under the control of quorum sensing (QS), a process of cell-to-cell communication to regulate group behaviors [3]. Compared with traditional antibiotics, interfering with QS systems is a novel means to effectively reduce virulence and combat P. aeruginosa infections with less selective pressure, meaning that it is much harder for the bacteria to develop drug resistance.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
