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

Abstract

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.

The Impact of an Efflux Pump Inhibitor on the Activity of Free and Liposomal Antibiotics against Pseudomonas aeruginosa

“…Unexpectedly, none of our treatments showed significant reductions in the production of AHLs in both strains, even though virulence factors controlled by QS seemed to have been reduced. Similar studies report a reduction in QS signal levels in P. aeruginosa by subinhibitory concentrations of antibiotics or adjuvants [72][73][74][75]. El-Shaer et al, for example, reported a reduction in QS signals with PABN alone in P. aeruginosa strains isolated from urinary tract and wound infections [43].…”

Quorum Sensing Inhibiting Activity of Cefoperazone and Its Metallic Derivatives on Pseudomonas aeruginosa

“…The untreated strains were also grown under the same conditions. Assay of different virulence factors was performed in the presence and absence of the tested compounds ( El-Mowafy et al., 2017 ).…”

“…QSI activity of azithromycin ( Tateda et al., 2001 ), doxycycline ( Husain and Ahmad, 2013 ), and ciprofloxacin ( Skindersoe et al., 2008 ) have been detected ( Nalca et al., 2006 ). Moreover, β-lactams, ceftazidime, cefepime and imipenem have demonstrate QSI activity at sub-inhibitory concentrations ( Skindersoe et al., 2008 ; El-Mowafy et al., 2017 ; Aleanizy et al., 2021 ).…”

<p>Quorum Quenching: A Potential Target for Antipseudomonal Therapy</p>

“…Pyocyanin secretion, the expression of genes lasB, rhlA, lasI, lasR, rhlI, and rhlR genes and production of biofilm [160] Manilkara zapota Pyocyanin, protease and elastase secretion and production of biofilm [151] Diarylheptanoids from the barks of Alnus viridis and Alnus glutinosa Pyocyanin secretion, twitching motility and production of biofilm [161] Gingerol Exoprotease, rhamnolipid and pyocyanin secretion and biofilm formation [162] Diterpene phytol Pyocyanin secretion, twitching motility and production of biofilm [163] Dovepress antibiotics can reduce the pathogenic factors' expression of P. aeruginosa such as the diminished of exotoxin A secretion, pyocyanin, protease, DNase, and phospholipase C, as well as significantly removing the QS activity of P. aeruginosa. 125 In addition, SICs of tobramycin could block the expressions of rhlI and rhlR genes by decreasing C4-HSL generation. Previous studies have also confirmed the impact of tobramycin, as a signaling molecule, on virulence genes expression in the transcriptional step.…”

“… 124 The SICs of macrolides and β-lactam antibiotics can reduce the pathogenic factors’ expression of P. aeruginosa such as the diminished of exotoxin A secretion, pyocyanin, protease, DNase, and phospholipase C, as well as significantly removing the QS activity of P. aeruginosa . 125 In addition, SICs of tobramycin could block the expressions of rhlI and rhlR genes by decreasing C4-HSL generation. Previous studies have also confirmed the impact of tobramycin, as a signaling molecule, on virulence genes expression in the transcriptional step.…”