Chlorogenic acid attenuates virulence factors and pathogenicity of Pseudomonas aeruginosa by regulating quorum sensing
Quorum sensing (QS) is a cell-to-cell communication that is used by bacteria to regulate collective behaviors. Quorum sensing controls virulence factor production in many bacterial species and it is regarded as an attractive target to combat bacterial pathogenicity, especially against antibiotic-resistant bacteria. Chlorogenic acid (CA), abundant in fruits, vegetables, and Chinese herbs, processes multiple activities. In this research, we explored its quorum sensing quenching activity. In Pseudomonas aeruginosa, CA significantly inhibited the formation of biofilm, the ability of swarming, and virulence factors including protease and elastase activities and rhamnolipid and pyocyanin production. CA showed similar inhibitory effects in Chromobacterium violaceum on its biofilm formation, swarming motility, chitinolytic activity and violacein production. We examined the expression of QS-related genes in P.aeruginosa and found these genes were all downregulated by CA treatment. Computational modeling revealed that CA can form hydrogen bonds with all three QS receptors. Caenorhabditis elegans and mouse infection models were employed to explore the anti-virulence ability of CA and its effect on pathogenesis process in vivo. CA extended the survival period and reduced the quantity of P. aeruginosa in nematode gut, showing a moderate protective effect on C. elegans. In mice wound model, CA-treated groups showed an accelerating healing rate and the bacteria number in wound area was also decreased by CA treatment. It is suggested by our research that CA has potential to be used as an anti-virulence factor in P. aeruginosa infection.
KeywordsChlorogenic acid Quorum sensing inhibitor Pseudomonas aeruginosa Anti-virulence
The present study was supported by the National Natural Science Foundation of China (Grant Nos. 81301902, 81773837), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Double First - Class Uiversity Project (CPU2018GY14, CPU2018GY15).
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no competing interests.
All studies were performed in compliance with the National Institutes of Health Guide for the Care and Use of laboratory Animals and approved by IACUC (Institutional Animal Care and Use Committee of China Pharmaceutical University).
- Cirioni O, Mocchegiani F, Cacciatore I, Vecchiet J, Silvestri C, Baldassarre L, Ucciferri C, Orsetti E, Castelli P, Provinciali M, Vivarelli M, Fornasari E, Giacometti A (2013) Quorum sensing inhibitor FS3-coated vascular graft enhances daptomycin efficacy in a rat model of staphylococcal infection. Peptides 40:77–81CrossRefGoogle Scholar
- Jorgensen JH (1993) Antimicrobial susceptibility testing of bacteria that grow aerobically. Infect Dis Clin N Am 7(2):393–409Google Scholar
- Kuo D, Yu G, Hoch W, Gabay D, Long L, Ghannoum M, Nagy N, Harding CV, Viswanathan R, Shoham M (2015) Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to beta-lactam antibiotics. Antimicrob Agents Chemother 59(3):1512–1518CrossRefGoogle Scholar
- McClean KH, Winson MK, Fish L, Taylor A, Chhabra SR, Camara M, Daykin M, Lamb JH, Swift S, Bycroft BW, Stewart GS, Williams P (1997) Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones. Microbiology 143(Pt 12):3703–3711CrossRefGoogle Scholar
- Prithiviraj B, Bais HP, Weir T, Suresh B, Najarro EH, Dayakar BV, Schweizer HP, Vivanco JM (2005) Down regulation of virulence factors of Pseudomonas aeruginosa by salicylic acid attenuates its virulence on Arabidopsis thaliana and Caenorhabditis elegans. Infect Immun 73(9):5319–5328CrossRefGoogle Scholar
- Rumbaugh KP, Griswold JA, Iglewski BH, Hamood AN (1999) Contribution of quorum sensing to the virulence of Pseudomonas aeruginosa in burn wound infections. Infect Immun 67(11):5854–5862Google Scholar
- Simonetti O, Cirioni O, Cacciatore I, Baldassarre L, Orlando F, Pierpaoli E, Lucarini G, Orsetti E, Provinciali M, Fornasari E, Di Stefano A, Giacometti A, Offidani A (2016) Efficacy of the quorum sensing inhibitor FS10 alone and in combination with tigecycline in an animal model of Staphylococcal infected wound. PLoS One 11(6):e0151956CrossRefGoogle Scholar
- Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31(2):455–461Google Scholar
- Wang L, Bi C, Cai H, Liu B, Zhong X, Deng X, Wang T, Xiang H, Niu X, Wang D (2015) The therapeutic effect of chlorogenic acid against Staphylococcus aureus infection through sortase A inhibition. Front Microbiol 6:1031Google Scholar
- Wikler MA (1990) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. Clinical & Laboratory Standards InstituteGoogle Scholar