Abstract
Antibiotic resistance for a large diversity of clinically significant pathogens has been observed with increasing frequency over the past several decades. This pervasive issue isĀ one of the most serious public health concerns of this century. Clinicians and researchers have been persuaded to develop innovative techniques to manage harmful microorganisms to address this problem. The bacterial virulence genes are mostly in the monitoring purview of quorum sensing signal molecules, called autoinducers, and are expressed only when the signal is beyond a threshold which is determined by the bacterial cell density. Hence, interfering with these signals will effectively silence the operon that harbors virulence genes, without being detrimental to bacteria so that there is no selective pressure. This interpolation with quorum sensing paths of microbes, known as antipathogenic and/or anti-virulence strategies, is one of several such promising approaches which mainly focus on disruption of bacterial pathogenicity and does not involve bacterial killing. Inhibition of indicator molecules is accomplished by signal dilapidation, use of natural or synthetic analogues, and various other strategies which are described in this chapter. Also discussed are the modes of action of bacterial quorum sensing and an overview of potential sources of bioactive components as QS inhibitors.
Similar content being viewed by others
References
Atkinson, S., Chang, C.-Y., Sockett, R. E., CĆ”mara, M., & Williams, P. (2006). Quorum sensing in yersinia enterocolitica controls swimming and swarming motility. Journal of Bacteriology, 188, 1451ā1461. https://doi.org/10.1128/JB.188.4.1451-1461.2006
Bijtenhoorn, P., Mayerhofer, H., MĆ¼ller-Dieckmann, J., Utpatel, C., Schipper, C., Hornung, C., et al. (2011). A novel metagenomic short-chain dehydrogenase/reductase attenuates pseudomonas aeruginosa biofilm formation and virulence on caenorhabditis elegans. PLoS One, 6, e26278. https://doi.org/10.1371/Journal.Pone.0026278
Boylan, M., Miyamoto, C., Wall, L., Graham, A., & And Meighen, E. (1989). Lux C, D and E genes of the Vibrio fischeri luminescence operon code for the reductase, transferase, and synthetase enzymes involved in aldehyde biosynthesis. Photochemistry and Photobiology, 49, 681ā688. https://doi.org/10.1111/J.1751-1097.1989.TB08441.X
Case, R. J., Labbate, M., & Kjelleberg, S. (2008). AHL-driven quorum-sensing circuits: Their frequency and function among the Proteobacteria. The ISME Journal, 24(2), 345ā349. https://doi.org/10.1038/ismej.2008.13
Chowdhary, P. K., Keshavan, N., Nguyen, H. Q., Peterson, J. A., GonzĆ”lez, J. E., & Haines, D. C. (2007). Bacillus megaterium CYP102A1 oxidation of acyl homoserine lactones and acyl homoserines. Biochemistry, 46, 14429ā14437. https://doi.org/10.1021/BI701945J
Chung, J., Goo, E., Yu, S., Choi, O., Lee, J., Kim, J., et al. (2011). Small-molecule inhibitor binding to an N-acyl-homoserine lactone synthase. Proceedings of the National Academy of Sciences of the United States of America, 108, 12089ā12094. https://doi.org/10.1073/PNAS.1103165108/-/DCSUPPLEMENTAL
Clarke, M. B., Hughes, D. T., Zhu, C., Boedeker, E. C., & Sperandio, V. (2006). The QseC sensor kinase: A bacterial adrenergic receptor. Proceedings of the National Academy of Sciences of the United States of America, 103, 10420ā10425. https://doi.org/10.1073/PNAS.0604343103
De Kievit, T. R., & Iglewski, B. H. (2000). Bacterial quorum sensing in pathogenic relationships. Infection and Immunity, 68, 4839ā4849. https://doi.org/10.1128/IAI.68.9.4839-4849.2000/ASSET/0908D8CE-0CBE-47E2-8B90-12F53FBE8167/ASSETS/GRAPHIC/II0900701003.JPEG
de Kraker, M. E. A., Stewardson, A. J., & Harbarth, S. (2016). Will 10 million people die a year due to antimicrobial resistance by 2050? PLoS Medicine, 13, 1002184. https://doi.org/10.1371/JOURNAL.PMED.1002184
Defoirdt, T. (2018). Quorum-sensing systems as targets for antivirulence therapy. Trends in Microbiology, 26, 313ā328. https://doi.org/10.1016/J.TIM.2017.10.005
Defoirdt, T., & Sorgeloos, P. (2012). Monitoring of Vibrio harveyi quorum sensing activity in real time during infection of brine shrimp larvae. The ISME Journal, 6, 2314. https://doi.org/10.1038/ISMEJ.2012.58
Defoirdt, T., Boon, N., Sorgeloos, P., Verstraete, W., & Bossier, P. (2007). Quorum sensing and quorum quenching in Vibrio harveyi: Lessons learned from in vivo work. The ISME Journal, 21(2), 19ā26. https://doi.org/10.1038/ismej.2007.92
Deryabin, D., Galadzhieva, A., Kosyan, D., & Duskaev, G. (2019). Plant-derived inhibitors of AHL-mediated quorum sensing in bacteria: Modes of action. International Journal of Molecular Sciences, 20. https://doi.org/10.3390/IJMS20225588
Eberhard, A., Burlingame, A. L., Eberhard, C., Kenyon, G. L., Nealson, K. H., & Oppenheimer, N. J. (1981). Structural identification of autoinducer of Photobacterium fischeri luciferase. Biochemistry, 20, 2444ā2449. https://doi.org/10.1021/BI00512A013
Eberl, L. (1999). N-acyl homoserinelactone-mediated gene regulation in gram-negative bacteria. Systematic and Applied Microbiology, 22, 493ā506. https://doi.org/10.1016/S0723-2020(99)80001-0
Fetzner, S. (2015). Quorum quenching enzymes. Journal of Biotechnology, 201, 2ā14. https://doi.org/10.1016/J.JBIOTEC.2014.09.001
Fong, J., Yuan, M., Jakobsen, T. H., Mortensen, K. T., Delos Santos, M. M. S., Chua, S. L., et al. (2017). Disulfide bond-containing Ajoene analogues as novel quorum sensing inhibitors of Pseudomonas aeruginosa. Journal of Medicinal Chemistry, 60, 215ā227. https://doi.org/10.1021/ACS.JMEDCHEM.6B01025/SUPPL_FILE/JM6B01025-SI002.CSV
Fuqua, W. C., Winans, S. C., & Greenberg, E. P. (1994). Quorum sensing in bacteria: The LuxR-LuxI family of cell density- responsive transcriptional regulators. Journal of Bacteriology, 176, 269ā275. https://doi.org/10.1128/jb.176.2.269-275.1994
Galloway, W. R. J. D., Hodgkinson, J. T., Bowden, S. D., Welch, M., & Spring, D. R. (2011). Quorum sensing in Gram-negative bacteria: Small-molecule modulation of AHL and AI-2 quorum sensing pathways. Chem. Rev. 111, 28ā67. https://doi.org/10.1021/CR100109T/ASSET/CR100109T.FP.PNG_V03.
Ganin, H., Rayo, J., Amara, N., Levy, N., Krief, P., & Meijler, M. M. (2012). Sulforaphane and erucin, natural isothiocyanates from broccoli, inhibit bacterial quorum sensing. MedChemComm, 4, 175ā179. https://doi.org/10.1039/C2MD20196H
George, E. A., & Muir, T. W. (2007). Molecular mechanisms of agr quorum sensing in virulent staphylococci. Chembiochem, 8, 847ā855. https://doi.org/10.1002/CBIC.200700023
Haque, S., Yadav, D. K., Bisht, S. C., Yadav, N., Singh, V., Dubey, K. K., et al. (2019). Quorum sensing pathways in gram-positive and -negative bacteria: Potential of their interruption in abating drug resistance. Journal of Chemotherapy, 31, 161ā187. https://doi.org/10.1080/1120009X.2019.1599175
Hentzer, M., & Givskov, M. (2003). Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. The Journal of Clinical Investigation, 112, 1300. https://doi.org/10.1172/JCI20074
Hinchliffe, S., Butcher, A., & Rahman, M. M. (2018). The AMR problem: Demanding economies, biological margins, and co-producing alternative strategies. Palgrave Communications, 41(4), 1ā12. https://doi.org/10.1057/s41599-018-0195-4
Kalia, V. C. (2013). Quorum sensing inhibitors: An overview. Biotechnology Advances, 31, 224ā245. https://doi.org/10.1016/j.biotechadv.2012.10.004
Kaufmann, G. F., Sartorio, R., Lee, S. H., Mee, J. M., Altobell, L. J., Kujawa, D. P., et al. (2006). Antibody interference with N-acyl Homoserine lactone-mediated bacterial quorum sensing. Journal of the American Chemical Society, 128, 2802. https://doi.org/10.1021/JA0578698
LaSarre, B., & Federle, M. J. (2013). Exploiting quorum sensing to confuse bacterial pathogens. Microbiology and Molecular Biology Reviews, 77, 73ā111. https://doi.org/10.1128/MMBR.00046-12
Leadbetter, J. R., & Greenberg, E. P. (2000). Metabolism of acyl-homoserine lactone quorum-sensing signals by Variovorax paradoxus. Journal of Bacteriology, 182, 6921ā6926. https://doi.org/10.1128/JB.182.24.6921-6926.2000/ASSET/660BF097-B3D9-4186-901F-B2F2FAF1BD90/ASSETS/GRAPHIC/JB2400663007.JPEG
Levy, D., Reichert, C. O., & Bydlowski, S. P. (2019). Paraoxonases activities and polymorphisms in elderly and old-age diseases: An overview. Antioxidants, 8, 118. https://doi.org/10.3390/ANTIOX8050118
Li, W. R., Ma, Y. K., Shi, Q. S., Xie, X. B., Sun, T. L., Peng, H., et al. (2018). Diallyl disulfide from garlic oil inhibits Pseudomonas aeruginosa virulence factors by inactivating key quorum sensing genes. Applied Microbiology and Biotechnology, 102, 7555ā7564. https://doi.org/10.1007/S00253-018-9175-2
LuĆs, Ć., Duarte, A., Pereira, L., & Domingues, F. (2017). Chemical profiling and evaluation of antioxidant and anti-microbial properties of selected commercial essential oils: A comparative study. Medicines (Basel, Switzerland), 4, 36. https://doi.org/10.3390/MEDICINES4020036
Martinelli, N., Consoli, L., Girelli, D., Grison, E., Corrocher, R., & Olivieri, O. (2013). Paraoxonases: Ancient substrate hunters and their evolving role in ischemic heart disease. Advances in Clinical Chemistry, 59, 65ā100. https://doi.org/10.1016/B978-0-12-405211-6.00003-6
McClean, K. H., Winson, M. K., Fish, L., Taylor, A., Chhabra, S. R., Camara, M., et al. (1997). Quorum sensing and Chromobacterium violaceum: Exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones. Microbiology, 143(Pt 12), 3703ā3711. https://doi.org/10.1099/00221287-143-12-3703
Miyairi, S., Tateda, K., Fuse, E. T., Ueda, C., Saito, H., Takabatake, T., et al. (2006). Immunization with 3-oxododecanoyl-L-homoserine lactone-protein conjugate protects mice from lethal Pseudomonas aeruginosa lung infection. Journal of Medical Microbiology, 55, 1381ā1387. https://doi.org/10.1099/JMM.0.46658-0
Mok, K. C., Wingreen, N. S., & Bassler, B. L. (2003). Vibrio harveyi quorum sensing: A coincidence detector for two autoinducers controls gene expression. The EMBO Journal, 22, 870ā881. https://doi.org/10.1093/EMBOJ/CDG085
Ng, W. L., & Bassler, B. L. (2009). Bacterial quorum-sensing network architectures. Annual Review of Genetics, 43, 197ā222. https://doi.org/10.1146/ANNUREV-GENET-102108-134304
Nielsen, A., Nielsen, K. F., Frees, D., Larsen, T. O., & Ingmer, H. (2010). Method for screening compounds that influence virulence gene expression in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 54, 509ā512. https://doi.org/10.1128/AAC.00940-09
Noor, A. O., Almasri, D. M., Basyony, A. F., Albohy, A., Almutairi, L. S., Alhammadi, S. S., et al. (2022). Biodiversity of N-acyl homoserine lactonase (aiiA) gene from Bacillus subtilis. Microbial Pathogenesis, 166, 105543. https://doi.org/10.1016/J.MICPATH.2022.105543
Park, J., Jagasia, R., Kaufmann, G. F., Mathison, J. C., Ruiz, D. I., Moss, J. A., et al. (2007). Infection control by antibody disruption of bacterial quorum sensing signaling. Chemistry & Biology, 14, 1119. https://doi.org/10.1016/J.CHEMBIOL.2007.08.013
Peeralil, S., Joseph, T. C., Murugadas, V., Akhilnath, P. G., Sreejith, V. N., & Lalitha, K. V. (2020). Vibrio harveyi virulence gene expression in vitro and in vivo during infection in black tiger shrimp Penaeus monodon. Diseases of Aquatic Organisms, 139, 153ā160. https://doi.org/10.3354/dao03475
Rasko, D. A., Moreira, C. G., De, R. L., Reading, N. C., Ritchie, J. M., Waldor, M. K., et al. (2008). Targeting QseC signaling and virulence for antibiotic development. Science, 321, 1078. https://doi.org/10.1126/SCIENCE.1160354
Rasmussen, T. B., Skindersoe, M. E., Bjarnsholt, T., Phipps, R. K., Christensen, K. B., Jensen, P. O., et al. (2005). Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology, 151, 1325ā1340. https://doi.org/10.1099/mic.0.27715-0
Rudrappa, T., & Bais, H. P. (2008). Curcumin, a known phenolic from Curcuma longa, attenuates the virulence of Pseudomonas aeruginosa PAO1 in whole plant and animal pathogenicity models. Journal of Agricultural and Food Chemistry, 56, 1955ā1962. https://doi.org/10.1021/JF072591J
Rutherford, S. T., & Bassler, B. L. (2012). Bacterial quorum sensing: Its role in virulence and possibilities for its control. Cold Spring Harbor Perspectives in Medicine, 2. https://doi.org/10.1101/cshperspect.a012427
Schaefer, A. L., Val, D. L., Hanzelka, B. L., Cronan, J. E., & Greenberg, E. P. (1996). Generation of cell-to-cell signals in quorum sensing: Acyl homoserine lactone synthase activity of a purified Vibrio fischeri LuxI protein. Proceedings of the National Academy of Sciences of the United States of America, 93, 9505. https://doi.org/10.1073/PNAS.93.18.9505
Sharma, R., & Jangid, K. (2015). Fungal quorum sensing inhibitors. In V. C. Kalia (Ed.), Quorum sensing vs quorum quenching: A battle with no end in sight (pp. 237ā257). Springer. https://doi.org/10.1007/978-81-322-1982-8_20
Shunmoogam, N., Naidoo, P., & Chilton, R. (2018). Paraoxonase (PON)-1: A brief overview on genetics, structure, polymorphisms and clinical relevance. Vascular Health and Risk Management, 14, 137ā143. https://doi.org/10.2147/VHRM.S165173
Skindersoe, M. E., Ettinger-Epstein, P., Rasmussen, T. B., Bjarnsholt, T., De Nys, R., & Givskov, M. (2008). Quorum sensing antagonism from marine organisms. Marine Biotechnology, 10, 56ā63. https://doi.org/10.1007/s10126-007-9036-y
Stevens, A. M., Queneau, Y., SoulĆØre, L., Von Bodman, S., & Doutheau, A. (2011). Mechanisms and synthetic modulators of AHL-dependent gene regulation. Chemical Reviews, 111, 4ā27. https://doi.org/10.1021/cr100064s
Stoltz, D. A., Ozer, E. A., Ng, C. J., Yu, J. M., Reddy, S. T., Lusis, A. J., et al. (2007). Paraoxonase-2 deficiency enhances Pseudomonas aeruginosa quorum sensing in murine tracheal epithelia. American Journal of Physiology. Lung Cellular and Molecular Physiology, 292. https://doi.org/10.1152/AJPLUNG.00370.2006
Tan, S. Y. Y., Liu, Y., Chua, S. L., Vejborg, R. M., Jakobsen, T. H., Chew, S. C., et al. (2014). Comparative systems biology analysis to study the mode of action of the isothiocyanate compound iberin on Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy, 58, 6648ā6659. https://doi.org/10.1128/AAC.02620-13/SUPPL_FILE/ZAC011143400SO1.PDF
Todd, D. A., Parlet, C. P., Crosby, H. A., Malone, C. L., Heilmann, K. P., Horswill, A. R., et al. (2017). Signal biosynthesis inhibition with ambuic acid as a strategy to target antibiotic-resistant infections. Antimicrobial Agents and Chemotherapy, 61. https://doi.org/10.1128/AAC.00263-17/SUPPL_FILE/ZAC008176432S1.PDF
Tu, K. C., & Bassler, B. L. (2007). Multiple small RNAs act additively to integrate sensory information and control quorum sensing in Vibrio harveyi. Genes & Development, 21, 221ā233. https://doi.org/10.1101/GAD.1502407
Uroz, S., & Heinonsalo, J. (2008). Degradation of N-acyl homoserine lactone quorum sensing signal molecules by forest root-associated fungi. FEMS Microbiology Ecology, 65, 271ā278. https://doi.org/10.1111/J.1574-6941.2008.00477.X
Utari, P. D., Vogel, J., & Quax, W. J. (2017). Deciphering physiological functions of AHL quorum quenching acylases. Frontiers in Microbiology, 8, 1123. https://doi.org/10.3389/FMICB.2017.01123/BIBTEX
Waters, C. M., & Bassler, B. L. (2006). The Vibrio harveyi quorum-sensing system uses shared regulatory components to discriminate between multiple autoinducers. Genes & Development, 20, 2754ā2767. https://doi.org/10.1101/GAD.1466506
Wei, Y., Perez, L. J., Ng, W. L., Semmelhack, M. F., & Bassler, B. L. (2011). Mechanism of vibrio cholerae autoinducer-1 biosynthesis. ACS Chemical Biology, 6, 356ā365. https://doi.org/10.1021/cb1003652
World Health Organization, and Food and Agriculture Organization of the United Nations. (2017). Global framework for development & stewardship to combat antimicrobial resistance. Available at: https://www.who.int/publications/m/item/global-framework-for-development-stewardship-to-combat-antimicrobial-resistance-draft-roadmap Accessed 23 Mar 2023.
Xavier, K. B., & Bassler, B. L. (2005). Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli. Journal of Bacteriology, 187, 238. https://doi.org/10.1128/JB.187.1.238-248.2005
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2023 Springer Nature Singapore Pte Ltd.
About this entry
Cite this entry
Peeralil, S., Narayanan, S.V., Joseph, T.C., Lalitha, K.V. (2023). Anti-virulence to Counter the AMR Conundrum: Principles and Strategies. In: Mothadaka, M.P., Vaiyapuri, M., Rao Badireddy, M., Nagarajrao Ravishankar, C., Bhatia, R., Jena, J. (eds) Handbook on Antimicrobial Resistance. Springer, Singapore. https://doi.org/10.1007/978-981-16-9723-4_44-1
Download citation
DOI: https://doi.org/10.1007/978-981-16-9723-4_44-1
Received:
Accepted:
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-9723-4
Online ISBN: 978-981-16-9723-4
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences