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J Appl Microbiol ; 117(5): 1388-99, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25175797

RESUMO

AIMS: Quorum sensing circuits regulate virulence factors in Pseudomonas aeruginosa and coordinate bacterial pathogenicity. We are interested in exploring available medications for their antiquorum sensing activity. METHODS AND RESULTS: First, we determined the MIC of ascorbate against Ps. aeruginosa strain PAO1, and all further experiments used concentrations below the MIC so that results could not be caused by reduced viability. Tests of subinhibitory concentrations of sodium ascorbate on cell signals were performed using a reporter strain assay. Sub-MICs of sodium ascorbate resulted in significant reduction of the signalling molecules C4-HSL and 3-oxo-C12-HSL (P < 0·01). The influence of sub-MIC of sodium ascorbate on virulence factors was also determined and ascorbate treatment led to significant depression of elastase, protease and haemolysin activities. In addition, inhibition of pyocyanin production, attenuation of biofilm formation and alteration of Pseudomonas motility was observed. Analysis by RT-PCR tested the effect of ascorbate on the expression of QS regulatory genes. Expression of QS regulatory genes, lasI, lasR, rhlI, rhlR, pqsR and pqsA, was repressed compared to untreated Ps. aeruginosa PAO1, confirming that ascorbate QS inhibition works on gene expression at the molecular level. CONCLUSION: Sodium ascorbate, even at low concentrations, inhibited QS and related virulence factors of Ps. aeruginosa PAO1. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that sodium ascorbate could function as signal modulator and virulence inhibitor in Ps. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Ácido Ascórbico/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Endopeptidases/farmacologia , Proteínas Hemolisinas/biossíntese , Locomoção/efeitos dos fármacos , Elastase Pancreática/biossíntese , Peptídeo Hidrolases/biossíntese , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , Piocianina/biossíntese , Percepção de Quorum/genética , Fatores de Virulência/metabolismo
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