Pharmacological Inhibition of Quorum Sensing for the Treatment of Chronic Bacterial Infections

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2003 Nov 5

PMID 14597754

Citations 195

Authors

Morten Hentzer

Michael Givskov

Affiliations

Soon will be listed here.

Abstract

Traditional treatment of infectious diseases is based on compounds that aim to kill or inhibit bacterial growth. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. The discovery of bacterial-communication systems (quorum-sensing systems), which orchestrate important temporal events during the infection process, has afforded a novel opportunity to ameliorate bacterial infection by means other than growth inhibition. Compounds able to override bacterial signaling are present in nature. Herein we discuss the known signaling mechanisms and potential antipathogenic drugs that specifically target quorum-sensing systems in a manner unlikely to pose a selective pressure for the development of resistant mutants.

Citing Articles

Innovative application of ceftriaxone as a quorum sensing inhibitor in Pseudomonas aeruginosa.

Naga N, El-Badan D, Mabrouk M, Rateb H, Ghanem K, Shaaban M Sci Rep. 2025; 15(1):5022.

PMID: 39934154 PMC: 11814147. DOI: 10.1038/s41598-025-87609-0.

Silent signals: how -acyl homoserine lactones drive oral microbial behaviour and health outcomes.

Zhao Z, Guo L, Shan W, Chu C, Zhang J Front Oral Health. 2024; 5:1484005.

PMID: 39703871 PMC: 11655462. DOI: 10.3389/froh.2024.1484005.

Understanding rhizospheric microbial dynamics in gladiolus corms through quorum sensing and quorum quenching for disease control and growth promotion.

Hameed A, Riaz K, Jameel S, Aslam H, Alam M, Zaheer M BMC Plant Biol. 2024; 24(1):996.

PMID: 39443878 PMC: 11515647. DOI: 10.1186/s12870-024-05722-0.

Quorum Sensing Inhibitors: An Alternative Strategy to Win the Battle against Multidrug-Resistant (MDR) Bacteria.

Hetta H, Ramadan Y, Rashed Z, Alharbi A, Alsharef S, Alkindy T Molecules. 2024; 29(15).

PMID: 39124871 PMC: 11313800. DOI: 10.3390/molecules29153466.

Nanomaterials Regulate Bacterial Quorum Sensing: Applications, Mechanisms, and Optimization Strategies.

Hu C, He G, Yang Y, Wang N, Zhang Y, Su Y Adv Sci (Weinh). 2024; 11(15):e2306070.

PMID: 38350718 PMC: 11022734. DOI: 10.1002/advs.202306070.

References

Huber B, Riedel K, Hentzer M, Heydorn A, Gotschlich A, Givskov M . The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility. Microbiology (Reading). 2001; 147(Pt 9):2517-2528. DOI: 10.1099/00221287-147-9-2517. View

Xavier K, Bassler B . LuxS quorum sensing: more than just a numbers game. Curr Opin Microbiol. 2003; 6(2):191-7. DOI: 10.1016/s1369-5274(03)00028-6. View

Manefield M, de Nys R, Naresh K, Roger R, Givskov M, Peter S . Evidence that halogenated furanones from Delisea pulchra inhibit acylated homoserine lactone (AHL)-mediated gene expression by displacing the AHL signal from its receptor protein. Microbiology (Reading). 1999; 145 ( Pt 2):283-291. DOI: 10.1099/13500872-145-2-283. View

Xu K, McFeters G, Stewart P . Biofilm resistance to antimicrobial agents. Microbiology (Reading). 2000; 146 ( Pt 3):547-549. DOI: 10.1099/00221287-146-3-547. View

Hartman G, Wise R . Quorum sensing: potential means of treating gram-negative infections?. Lancet. 1998; 351(9106):848-9. DOI: 10.1016/S0140-6736(05)70282-8. View

DArgenio D, Calfee M, Rainey P, Pesci E . Autolysis and autoaggregation in Pseudomonas aeruginosa colony morphology mutants. J Bacteriol. 2002; 184(23):6481-9. PMC: 135425. DOI: 10.1128/JB.184.23.6481-6489.2002. View

Yates E, Philipp B, Buckley C, Atkinson S, Chhabra S, Sockett R . N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl chain length-dependent manner during growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa. Infect Immun. 2002; 70(10):5635-46. PMC: 128322. DOI: 10.1128/IAI.70.10.5635-5646.2002. View

Dong Y, Xu J, Li X, Zhang L . AiiA, an enzyme that inactivates the acylhomoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora. Proc Natl Acad Sci U S A. 2000; 97(7):3526-31. PMC: 16273. DOI: 10.1073/pnas.97.7.3526. View

Tateda K, Comte R, Pechere J, Kohler T, Yamaguchi K, van Delden C . Azithromycin inhibits quorum sensing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2001; 45(6):1930-3. PMC: 90577. DOI: 10.1128/AAC.45.6.1930-1933.2001. View

10.

Parsek M, Val D, Hanzelka B, Cronan Jr J, Greenberg E . Acyl homoserine-lactone quorum-sensing signal generation. Proc Natl Acad Sci U S A. 1999; 96(8):4360-5. PMC: 16337. DOI: 10.1073/pnas.96.8.4360. View

11.

Teplitski M, Robinson J, Bauer W . Plants secrete substances that mimic bacterial N-acyl homoserine lactone signal activities and affect population density-dependent behaviors in associated bacteria. Mol Plant Microbe Interact. 2000; 13(6):637-48. DOI: 10.1094/MPMI.2000.13.6.637. View

12.

Costerton J, Stewart P, Greenberg E . Bacterial biofilms: a common cause of persistent infections. Science. 1999; 284(5418):1318-22. DOI: 10.1126/science.284.5418.1318. View

13.

Passador L, Tucker K, Guertin K, Journet M, Kende A, Iglewski B . Functional analysis of the Pseudomonas aeruginosa autoinducer PAI. J Bacteriol. 1996; 178(20):5995-6000. PMC: 178457. DOI: 10.1128/jb.178.20.5995-6000.1996. View

14.

Riedel K, Hentzer M, Geisenberger O, Huber B, Steidle A, Wu H . N-acylhomoserine-lactone-mediated communication between Pseudomonas aeruginosa and Burkholderia cepacia in mixed biofilms. Microbiology (Reading). 2001; 147(Pt 12):3249-62. DOI: 10.1099/00221287-147-12-3249. View

15.

Passador L, Cook J, Gambello M, Rust L, Iglewski B . Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication. Science. 1993; 260(5111):1127-30. DOI: 10.1126/science.8493556. View

16.

Davies D, Parsek M, Pearson J, Iglewski B, Costerton J, Greenberg E . The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science. 1998; 280(5361):295-8. DOI: 10.1126/science.280.5361.295. View

17.

Lewenza S, Conway B, Greenberg E, Sokol P . Quorum sensing in Burkholderia cepacia: identification of the LuxRI homologs CepRI. J Bacteriol. 1999; 181(3):748-56. PMC: 93439. DOI: 10.1128/JB.181.3.748-756.1999. View

18.

Smith K, Bu Y, Suga H . Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic autoinducer analogs. Chem Biol. 2003; 10(1):81-9. DOI: 10.1016/s1074-5521(03)00002-4. View

19.

Gallagher L, McKnight S, Kuznetsova M, Pesci E, Manoil C . Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa. J Bacteriol. 2002; 184(23):6472-80. PMC: 135424. DOI: 10.1128/JB.184.23.6472-6480.2002. View

20.

Fenical W . New pharmaceuticals from marine organisms. Trends Biotechnol. 1997; 15(9):339-41. DOI: 10.1016/S0167-7799(97)01081-0. View