Inhibition of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells by quorum sensing autoinducer-mimics

Morkunas, Bernardas; Galloway, Warren R. J. D.; Wright, Megan H.; Ibbeson, Brett M.; Hodgkinson, James T.; O’Connell, Kieron M. G.; Bartolucci, Noemi; Valle, Martina Della; Welch, Martin; Spring, David R.

doi:10.1039/c2ob26501j

Cited by 73 publications

(88 citation statements)

References 59 publications

(173 reference statements)

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“…The following compounds were synthesized as previously described: CL, CTL, mBTL, mCTL (21), itc-13 (20), and PD-12 (36). See SI Appendix for complete synthesis and evaluation methods.…”

Section: Methodsmentioning

confidence: 99%

A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

O’Loughlin

Miller²,

Siryaporn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

642

550

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Quorum sensing is a chemical communication process that bacteria use to regulate collective behaviors. Disabling quorum-sensing circuits with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. The human pathogen Pseudomonas aeruginosa uses quorum sensing to control virulence and biofilm formation. Here, we analyze synthetic molecules for inhibition of the two P. aeruginosa quorum-sensing receptors, LasR and RhlR. Our most effective compound, meta-bromo-thiolactone (mBTL), inhibits both the production of the virulence factor pyocyanin and biofilm formation. mBTL also protects Caenorhabditis elegans and human lung epithelial cells from killing by P. aeruginosa. Both LasR and RhlR are partially inhibited by mBTL in vivo and in vitro; however, RhlR, not LasR, is the relevant in vivo target. More potent antagonists do not exhibit superior function in impeding virulence. Because LasR and RhlR reciprocally control crucial virulence factors, appropriately tuning rather than completely inhibiting their activities appears to hold the key to blocking pathogenesis in vivo.

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“…The following compounds were synthesized as previously described: CL, CTL, mBTL, mCTL (21), itc-13 (20), and PD-12 (36). See SI Appendix for complete synthesis and evaluation methods.…”

Section: Methodsmentioning

confidence: 99%

A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

O’Loughlin

Miller²,

Siryaporn

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

642

550

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“…LasI is the synthase for the autoinducer N-(3-oxododecanoyl) homoserine lactone (3OC12-HSL), while RhlI synthesizes the autoinducer N-butyryl homoserine lactone (C4-HSL). At high cell density, 3OC12-HSL and C4-HSL reach critical levels and activate their regulators, which in turn enhance the transcription of different virulence genes [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Antibiotic Resistance Profiles and Quorum Sensing-Dependent Virulence Factors in Clinical Isolates of Pseudomonas Aeruginosa

Wang

Gui

et al. 2013

Indian J Microbiol

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Pseudomonas aeruginosa produces multiple virulence factors that have been associated with quorum sensing. The aim of this study was to evaluate the prevalence of drug resistant profiles and quorum sensing related virulence factors. Pseudomonas aeruginosa were collected from different patients hospitalized in China, the isolates were tested for their susceptibility to different common antimicrobial drugs and detected QS-related virulence factors. We identified 170 isolates displaying impaired phenotypic activity, approximately 80 % of the isolates were found to exhibit the QS-dependent phenotypes, among them, 12 isolates were defective in AHLs production, and therefore considered QS-deficient strains. Resistance was most often observed to Cefazolin (81.2 %), followed by trimethoprim-sulfamethoxazole (73.5 %), ceftriaxone (62.4 %) and Cefotaxime, Levofloxacin, Ciprofloxacin (58.8 %), and to a lesser extent Meropenem (20.0 %), Cefepime (18.8 %), and Cefoperazone/sulbactam (2.4 %) The QS-deficient isolates that were negative for virulence factor production were generally less susceptible to the antimicrobials. The results showed a high incidences of antibiotic resistance and virulence properties in P. aeruginosa, and indicate that the clinical use of QS-inhibitory drugs that appear superior to conventional antimicrobials by not exerting any selective pressure on resistant strains.

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“…Direct antagonists of QS in P. aeruginosa have a great impact on the production of pyocyanin 31 . In this study, the level of pyocyanin was significantly reduced (P<0.01) with sub-MICs of cefepime, ceftazidime and imipenem (Fig.…”

mentioning

confidence: 99%

Quorum sensing inhibitory activity of sub-inhibitory concentrations of β-lactams

El-Mowafy

Galil

Habib³

et al. 2017

Afr H. Sci.

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Introduction: The virulence factors of Pseudomonas aeruginosa are under the control of quorum sensing (QS) signals. Hence, interference with QS prevents its pathogenesis. Objective: The aim of the present research is to assess the influence of some β-lactam antibiotics on cell communication and the release of different virulence factors. Methods: The minimal inhibitory concentrations of ceftazidime, cefepime and imipenem were evaluated by microbroth dilution method. The effect of sub-inhibitory concentration of the tested antibiotics on QS signals was investigated using reporter strain assay. In addition, different virulence factors (elastase, protease, pyocyanin and hemolysin) were estimated in the presence of their sub-inhibitory concentrations. Results: Low concentrations of ceftazidime, cefepime and imipenem caused significant elimination of the QS signals 3OH-C12-HSL and C4-HSL up to 1/20 MIC. Furthermore, low concentrations of the tested antimicrobials suppressed virulence factors elastase and hemolysin. Moreover, 1/20 of their MICs reduced elastase, protease, pyocyanin and hemolysin. Conclusion: Utilization of β-lactam antibiotics at low concentrations could be an effective approach for prevention and treatment of P. aeruginosa infection.

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Inhibition of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells by quorum sensing autoinducer-mimics

Cited by 73 publications

References 59 publications

A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

Antibiotic Resistance Profiles and Quorum Sensing-Dependent Virulence Factors in Clinical Isolates of Pseudomonas Aeruginosa

Quorum sensing inhibitory activity of sub-inhibitory concentrations of β-lactams

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