Abstract
The present study intended to decipher the anti-infective potential of bioactive phytocompounds, such as rosmarinic acid, morin, naringin, chlorogenic acid, and mangiferin, against aquatic and human bacterial pathogens using Artemia spp. nauplii and Caenorhabditis elegans as animal models, respectively. Initially, the test compounds were screened against the QS traits in Vibrio spp., such as bioluminescence production and biofilm formation. The test compounds effectively inhibited the bioluminescence in V. harveyi. Further, the confocal laser scanning microscopic analysis revealed that these natural compounds could efficiently reduce the clumping morphology, a characteristic biofilm formation in Vibrio spp., without inhibiting bacterial growth. The results of in vivo analysis showed a significant increase in the survival of Artemia spp. nauplii infected with Vibrio spp. upon exposure to these compounds. Moreover, the compounds used in this study were already proven and reported for their quorum sensing inhibitory efficacy against Pseudomonas aeruginosa. Hence, the anti-infective efficacy of these compounds against P. aeruginosa (PAO1) and its clinical isolates (AS1 and AS2) was studied using C. elegans as a live animal model system. The results of time-killing assay deciphered that rosmarinic acid and naringin are being the most effective ones in rescuing the animals from P. aeruginosa infection followed by morin, mangiferin, and chlorogenic acid. Further, the toxicity results revealed that these compounds did not show any lethal effect on C. elegans and Artemia spp. nauplii at the tested concentrations. In conclusion, the phytochemicals used in this study were effective in controlling the QS-regulated virulence traits in Vibrio spp. and P. aeruginosa infections in Artemia spp. nauplii and C. elegans animal model systems, respectively.
Graphical abstract
Similar content being viewed by others
Data availability
All the authors have contributed to this research work and approved the submission. The data supporting this study’s findings are available with the authors. Data are not publically available; however, it is available from the authors upon reasonable request.
References
Abirami G, Alexpandi R, Durgadevi R, Kannappan A, Veera Ravi A (2020) Inhibitory effect of morin against Candida albicans pathogenicity and virulence factor production: an in vitro and in vivo approaches. Front Microbiol 11:561298. https://doi.org/10.3389/fmicb.2020.561298
Ali M, Sun Y, Xie L, Yu H, Bashir A, Li L (2016) The pathogenicity of Pseudomonas syringae MB03 against Caenorhabditis elegans and the transcriptional response of nematicidal genes upon different nutritional conditions. Front Microbiol 7:805. https://doi.org/10.3389/fmicb.2016.00805
Annapoorani A, Jabbar AKKA, Musthafa SKS, Pandian SK, Ravi AV (2012a) Inhibition of quorum sensing mediated virulence factors production in urinary pathogen Serratia marcescens PS1 by marine sponges. Indian J Microbiol 52:160–166
Annapoorani A, Parameswari R, Pandian SK, Ravi AV (2012b) Methods to determine antipathogenic potential of phenolic and flavonoid compounds against urinary pathogen Serratia marcescens. J Microbiol Methods 9:208–211
Annapoorani A, Umamageswaran V, Parameswari R, Pandian SK, Ravi AV (2012c) Computational discovery of putative quorum sensing inhibitors against LasR and RhlR receptor proteins of Pseudomonas aeruginosa. J Comput Aided Mol Des 26:1067–1077
Bassler BL, Wright M, Showalter RE, Silverman MR (1993) Intercellular signaling in Vibrio harveyi sequence and function of genes regulating expression of luminescence. Mol Microbiol 9:773–786
Bosgelmez GT (2003) Quorum sensing in Gram-negative bacteria. Turk J Biol 27:85–93
Brackman G, Defoirdt T, Miyamoto C, Bossier P, Calenbergh SV, Nelis H, Coenye T (2008) Cinnamaldehyde and cinnamaldehyde derivatives reduce virulence in Vibrio spp. by decreasing the DNA-binding activity of the quorum sensing response regulator LuxR. BMC Microbiol 8:149
Brock JA, Bullis R (2001) Disease prevention and control for gametes and embryos of fish and marine shrimp. Aquaculture 197:137–159
Cabello FC (2006) Heavy use of prophylactic antibiotics in aquaculture: a growing problem for human and animal health and for the environment. Environ Microbiol 8:1137–1144
Chatterjee S, Haldar S (2012) Vibrio related diseases in aquaculture and development of rapid and accurate identification methods. J Mar Sci Res Dev S. https://doi.org/10.4172/2155-9910.S1-002. 1:002.
Croxatto A, Lauritz J, Chen C, Milton DL (2007) Vibrio anguillarum colonization of rainbow trout integument requires a DNA locus involved in exopolysaccharide transport and biosynthesis. Environ Microbiol 9:370–382
Defoirdt T, Boon N, Bossier P, Verstraete W (2004) Disruption of bacterial quorum sensing: an unexplored strategy to fight infections in aquaculture. Aquaculture 240:69–88
Defoirdt T, Crab R, Wood TK, Sorgeloos P, Verstraete W, Bossier P (2006) Quorum sensing-disrupting brominated furanones protect the gnotobiotic brine shrimp Artemia franciscana from pathogenic Vibrio harveyi, Vibrio campbellii and Vibrio parahaemolyticus isolates. Appl Environ Microbiol 72:6419–6423
Defoirdt T, Boon N, Sorgeloos P, Verstraete W, Bossier P (2008) Quorum sensing and quorum quenching in Vibrio harveyi: lessons learned from in vivo work. ISME J 2:19–26
Estrela AB, Abraham WR (2010) Combining biofilm-controlling compounds and antibiotics as a promising new way to control biofilm infections. Pharmaceuticals 3:1374–1393
Givskov M, de Nys R, Manefield M, Gram L, Maximilien R, Eberl L, Molin S, Steinberg PD, Kjelleberg S (1996) Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling. J Bacteriol 178:6618–6622
Grommen R, Verstraete W (2002) Environmental biotechnology: the ongoing quest. J Biotechnol 98:113–123
Guzman GA, Ruiz HM, Ascencio F (2004) A review of extracellular virulence product of Vibrio species important in disease of cultivated shrimp. Aquacult Res 35:1395–1404
Guzman JPMD, Yatip P, Soowannayan C, Maningasa MBB (2022) Piper betle L. leaf extracts inhibit quorum sensing of shrimp pathogen Vibrio harveyi and protect Penaeus vannamei post larvae against bacterial infection. Aquaculture 547:737452
Hameed ASS, Rahaman KH, Alagan A, Yoganandhan K (2003) Antibiotic resistance in bacteria isolated from hatchery-reared larvae and post-larvae of Macrobrachium rosenbergii. Aquaculture 217:39–48
Irazoqui JE, Troemel ER, Feinbaum RL, Luhachack LG, Cezairliyan BO, Ausubel FM (2010) Distinct pathogenesis and host responses during infection of C. elegans by P. aeruginosa and S. aureus. PLoS Pathog 6:e1000982. https://doi.org/10.1371/journal.ppat.1000982
Joint I, Tait K, Callow ME, Callow JA, Milton D, Williams P, Camara M (2002) Cell-to-cell communication across the prokaryote–eukaryote boundary. Science 298:1207
Kandasamy S, Khan W, Evans F, Crotchety A, Prithiviraj B (2012) A product of Ascophyllum nodosum enhances immune response of Caenorhabditis elegans against Pseudomonas aeruginosa infection. Mar Drugs 10:84–105
Kim SY, Lee SE, Kim YR, Kim CM, Ryu PY, Choy H, Chung SS, Rhee JH (2003) Regulation of Vibrio vulnificus virulence by the LuxS quorum-sensing system. Mol Microbiol 48:1647–1664
Kim W, Hendricks GL, Lee K, Mylonakis E (2017) An update on the use of C. elegans for preclinical drug discovery: screening and identifying anti-infective drugs. Expert Opin Drug Discov 12(6):625–633
Lilley BN, Bassler BL (2000) Regulation of quorum sensing in Vibrio harveyi by LuxO and Sigma-54. Mol Microbiol 36:940–954
Lynch MJ, Swift S, Kirke DF, Keevil CW, Dodd CE, Williams P (2002) The regulation of biofilm development by quorum sensing in Aeromonas hydrophila. Environ Microbiol 4:18–28
Manefield M, Harris L, Rice SA, De Nys R, Kjelleberg S (2000) Inhibition of luminescence and virulence in the black tiger prawn (Penaeus monodon) pathogen Vibrio harveyi by intercellular signal antagonists. Appl Environ Microbiol 66:2079–2084
Milton DL, Hardman A, Camara M, Chhabra SR, Bycroft BW, Stewart GSAB, Williams P (1997) Quorum sensing in Vibrio anguillarum: characterization of the vanI/vanR locus and identification of the autoinducer N-(3-oxodecanoyl)-homoserine lactone. J Bacteriol 179:3004–3012
Moal VLL, Servin AL (2006) The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides and microbiota. Clin Microbiol Rev 19:315–337
Molina-Aja A, Garcia-Gasca A, Abreu-Grobois A, Bolan-Mejia C, Roque A, Gomez-Gil B (2002) Plasmid profiling and antibiotic resistance of Vibrio strains isolated from cultured penaeid shrimp. FEMS Microbiol Lett 213:7–12
Musthafa KS, Sivamaruthi BS, Pandian SK, Ravi AV (2012b) Quorum sensing inhibition in Pseudomonas aeruginosa PAO1 by antagonistic compound phenyl acetic acid. Curr Microbiol 65:475–480
Nakai T, Park SC (2002) Bacteriophage therapy of infectious diseases in aquaculture. Res Microbiol 153:13–18
Naylor RL, Goldburg RJ, Primavera JH, Kautsky N, Beveridge MCM, Clay J, Folke C, Lubchenco J, Mooney H, Troell M (2000) Effect of aquaculture on world fish supplies. Nature 405:1017–1024
Nealson KH, Platt T, Hastings JW (1970) Cellular control of the synthesis and activity of the bacterial luminescent system. J Bacteriol 104:313–322
Nithya C, Pandian SK (2010) The in vitro antibiofilm activity of selected marine bacterial culture supernatants against Vibrio spp. Arch Microbiol 192:843–854
Pesci EC, Milbank JBJ, Pearson JP, McKnight S, Kende AS, Greenberg EP, Iglewski BH (1999) Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa. Proc Natl Acad Sci USA 96:11229–11234
Ravi AV, Musthafa KS, Jegathammbal G, Kathiresan K, Pandian SK (2007) Screening and evaluation of probiotics as a biocontrol agent against pathogenic Vibrios in marine aquaculture. Lett Appl Microbiol 45:219–223
Ravindran D, Ramanathan S, Arunachalam K, Jeyaraj GP, Shunmugiah KP, Arumugam VR (2018) Phytosynthesized silver nanoparticles as anti-quorum sensing and antibiofilm agent against the nosocomial pathogen Serratia marcescens: an in vitro study. J Appl Microbiol 124(6):1425–1440
Ryan RP, Dow JM (2008) Diffusible signals and interspecies communication in bacteria. Microbiology 154:1845–1858
Sakuragi Y, Kolter R (2007) Quorum-sensing regulation of the biofilm matrix genes (pel) of Pseudomonas aeruginosa. J Bacteriol 189:5383–5386
Santhakumari S, Jayakumar R, Logalakshmi R, Prabhu NM, Nazar AK, Pandian SK, Ravi AV (2018) In vitro and in vivo effect of 2, 6-Di-tert-butyl-4-methylphenol as an antibiofilm agent against quorum sensing mediated biofilm formation of Vibrio spp. Int J Food Microbiol 281:60–71
Satish L, Santhakumari S, Gowrishankar S, Pandian SK, Ravi AV, Ramesh M (2017) Rapid biosynthesized AgNPs from Gelidiella acerosa aqueous extract mitigates quorum sensing mediated biofilm formation of Vibrio species: an in vitro and in vivo approach. Environ. Sci Pollut Res Int 24(35):27254–27268
Scott E, Holden-Dye L, O’Connor V, Wand ME (2020) Intra strain variation of the effects of gram-negative ESKAPE pathogens on intestinal colonization, host viability, and host response in the model organism Caenorhabditis elegans. Front Microbiol 10:3113. https://doi.org/10.3389/fmicb.2019.03113
Senturk S, Ulusoy S, Bosgelmez TG, Yagci A (2012) Quorum sensing and virulence of Pseudomonas aeruginosa during urinary tract infections. J Infect Dev Ctries 6:501–507
Smith RS, Iglewski BH (2003) Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. J Clin Invest 112:1460–1465
Srinivasan R, Santhakumari S, Ravi AV (2017) In vitro antibiofilm efficacy of Piper betle against quorum sensing mediated biofilm formation of luminescent Vibrio harveyi. Microb Pathog 110:232–239
Srinivasan R, Vigneshwari L, Rajavel T, Durgadevi R, Kannappan A, Balamurugan K, Devi KP, Ravi AV (2017) Biogenic synthesis of silver nanoparticles using Piper betle aqueous extract and evaluation of its anti-quorum sensing and antibiofilm potential against uropathogens with cytotoxic effects: an in vitro and in vivo approach. Environ Sci Pollut Res Int 25(11):0538–10554
Swift S, Karlyshev AV, Fish L, Durant EL, Winson MK, Chhabra SR, Williams P, Macintyre S, Stewart GS. (1997). Quorum sensing in Aeromonas hydrophila and Aeromonas salmonicida: identification of the LuxRI homologs AhyRI and AsaRI and their cognate N-acyl homoserine lactone signal molecules. J Bacteriol 179:5271–5281.
Tan MW, Mahajan-Miklos S, Ausubel FM (1999) Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci USA 96:715–720
Thenmozhi R, Nithyanand P, Rathna J, Pandian SK (2009) Antibiofilm activity of coral-associated bacteria against different clinical M serotypes of Streptococcus pyogenes. FEMS Immunol Med Microbiol 57:284–294
Vikram A, Jayaprakasha GK, Jesudhasan PR, Pillai SD, Patil BS (2010) Suppression of bacterial cell–cell signalling, biofilm formation and type III secretion system by citrus flavonoids. J Appl Microbiol 109:515–527
Vincent AT, Gauthier J, Derome N, Charette SJ (2019) The rise and fall of antibiotics in aquaculture. In: Derome N (ed) Microbial Communities in Aquaculture Ecosystems. Springer, Cham. https://doi.org/10.1007/978-3-030-16190-31.
Yildiz FH, Visick KL (2009) Vibrio biofilms: so much the same yet so different. Trends Microbiol 17:109–118
Funding
The authors AA, VB, BA, KA, SVPIA, SM, BK, and AV gratefully acknowledge the computational and bioinformatics facility provided by the Alagappa University Bioinformatics Infrastructure Facility (funded by the Department of Biotechnology, Government of India; Grant No. BT/BI/25/001/2006). AA gratefully acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi [Grant No. 9/688 (0014)/2011] and Dr. D. S. Kothari Post Doctoral Fellowship, UGC, New Delhi for the financial assistance rendered [Grant No: F.4 − 2/2006(BSR)/BL/18–19/0298]. AA gratefully acknowledges the Department of Zoology, University of Madras (Guindy Campus), Chennai, for the academic support under the DST-FIST scheme.
Author information
Authors and Affiliations
Contributions
AA, VB, and AV conceived and designed research, AA, VB and BA conducted experiments, and KA, SVPIA, and SM provided support to conduct the experiments and manuscript preparation. BK and AVR contribution of chemicals, Artemia spp. nauplii and C. elegans. AA wrote the manuscript. AVR and JS manuscript correction.
Corresponding author
Ethics declarations
Conflict of interest
There is no conflict of interest declared by all the authors of this manuscript.
Ethical approval
This article does not contain any studies with human participants or vertebrate animal models performed by any authors.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Angusamy, A., Balasubramanian, V., Arunmurugan, B. et al. Anti-infective potential of plant-derived quorum sensing inhibitors against multi-drug resistant human and aquatic bacterial pathogens. World J Microbiol Biotechnol 39, 147 (2023). https://doi.org/10.1007/s11274-023-03578-4
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11274-023-03578-4