Lu Dai1, Tian-Qi Wu2, Yi-Song Xiong3, Hong-Bing Ni4, Ye Ding5, Wen-Chen Zhang6, Shao-Peng Chu5, Shao-Qing Ju5, Juan Yu7. 1. Department of Laboratory Medicine, Affiliated Hospital of Nantong University, 20 Xi Si Road, Nantong, 226001, PR China; Department of Laboratory Medicine, Kunshan affiliated Hospital of Nanjing University of Chinese Medicine, 189 Chao Yang Road, Kunshan, 215300, PR China. 2. Glenelg Country School, 12793 Folly Quarter Rd, Ellicott City, MD, 21042, USA. 3. Department of Laboratory Medicine, Chengdu Military General Hospital, 270 Tian Hui Road, Chengdu, 610000, PR China. 4. Department of Business and External Cooperation, Affiliated Hospital of Nantong University, 20 Xi Si Road, Nantong, 226001, PR China. 5. Department of Laboratory Medicine, Affiliated Hospital of Nantong University, 20 Xi Si Road, Nantong, 226001, PR China. 6. Department of Clinical Laboratory, Wuxi Children's Hospita, No. 299 at Qingyang Road, Wuxi, 214023, PR China. 7. Department of Laboratory Medicine, Affiliated Hospital of Nantong University, 20 Xi Si Road, Nantong, 226001, PR China; Insitute of Public Health, Nantong University, 9 Se Yuan Road, Nantong, 226001, PR China. Electronic address: yujuanjs@163.com.
Abstract
AIMS: Pseudomonas aeruginosa is one of the leading causes of opportunistic and hospital-acquired infections worldwide, which is frequently linked with clinical treatment difficulties. Ibuprofen, a widely used non-steroidal anti-inflammatory drug, has been previously reported to exert antimicrobial activity with the specific mechanism. We hypothesized that inhibition of P. aeruginosa with ibuprofen is involved in the quorum sensing (QS) systems. MAIN METHODS: CFU was utilized to assessed the growth condition of P. aeruginosa. Crystal violent staining and acridine orange staining was used to evaluate the biofilm formation and adherence activity. The detection of QS virulence factors such as pyocyanin, elastase, protease, and rhamnolipids were applied to investigation the anti-QS activity of ibuprofen against P. aeruginosa. The production of 3-oxo-C12-HSL and C4-HSL was confirmed by liquid chromatography/mass spectrometry analysis. qRT-PCR was used to identify the QS-related gene expression. Furthermore, we explored the binding effects between ibuprofen and QS-associated proteins with molecular docking. KEY FINDINGS: Ibuprofen inhibits P. aeruginosa biofilm formation and adherence activity. And the inhibitory effects of ibuprofen on C4-HSL levels were concentration-dependent (p < 0.05), while it has no effect on 3-oxo-C12-HSL. Moreover, ibuprofen attenuates the production of virulence factors in P. aeruginosa (p < 0.05). In addition, the genes of QS system were decreased after the ibuprofen treatment (p < 0.05). Of note, ibuprofen was binding with LuxR, LasR, LasI, and RhlR at high binding scores. SIGNIFICANCE: The antibiofilm and anti-QS activity of ibuprofen suggest that it can be a candidate drug for the treatment of clinical infections with P. aeruginosa.
AIMS: Pseudomonas aeruginosa is one of the leading causes of opportunistic and hospital-acquired infections worldwide, which is frequently linked with clinical treatment difficulties. Ibuprofen, a widely used non-steroidal anti-inflammatory drug, has been previously reported to exert antimicrobial activity with the specific mechanism. We hypothesized that inhibition of P. aeruginosa with ibuprofen is involved in the quorum sensing (QS) systems. MAIN METHODS: CFU was utilized to assessed the growth condition of P. aeruginosa. Crystal violent staining and acridine orange staining was used to evaluate the biofilm formation and adherence activity. The detection of QS virulence factors such as pyocyanin, elastase, protease, and rhamnolipids were applied to investigation the anti-QS activity of ibuprofen against P. aeruginosa. The production of 3-oxo-C12-HSL and C4-HSL was confirmed by liquid chromatography/mass spectrometry analysis. qRT-PCR was used to identify the QS-related gene expression. Furthermore, we explored the binding effects between ibuprofen and QS-associated proteins with molecular docking. KEY FINDINGS:Ibuprofen inhibits P. aeruginosa biofilm formation and adherence activity. And the inhibitory effects of ibuprofen on C4-HSL levels were concentration-dependent (p < 0.05), while it has no effect on 3-oxo-C12-HSL. Moreover, ibuprofen attenuates the production of virulence factors in P. aeruginosa (p < 0.05). In addition, the genes of QS system were decreased after the ibuprofen treatment (p < 0.05). Of note, ibuprofen was binding with LuxR, LasR, LasI, and RhlR at high binding scores. SIGNIFICANCE: The antibiofilm and anti-QS activity of ibuprofen suggest that it can be a candidate drug for the treatment of clinical infections with P. aeruginosa.
Authors: Emmanuel T Oluwabusola; Nursheena Parveen Katermeran; Wee Han Poh; Teo Min Ben Goh; Lik Tong Tan; Oluwatofunmilayo Diyaolu; Jioji Tabudravu; Rainer Ebel; Scott A Rice; Marcel Jaspars Journal: Molecules Date: 2022-03-06 Impact factor: 4.411