Quorum Sensing System Lactones Do Not Increase Invasiveness of a MexAB‐OprM Efflux Mutant but Do Play a Partial Role in <i>Pseudomonas aeruginosa</i> Invasion

Kondo, Akira; Hirakata, Yoichi; Gotoh, Naomasa; Fukushima, Kazuko Y.; Yanagihara, Katsunori; Ohno, Hideaki; Higashiyama, Yasuhito; Miyazaki, Y; Nishide, Kiyoharu; Node, Manabu; Yamada, Yasuaki; Kohno, Shigeru; Kamihira, Shimeru

doi:10.1111/j.1348-0421.2006.tb03806.x

Cited by 7 publications

(3 citation statements)

References 20 publications

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“…The role of quorum sensing (QS) and biofilm formation in Pseudomonas aeruginosa biology is clear, and previous reports have suggested that knocking out QS systems in P. aeruginosa results in decreased virulence in animal models of infection [1], [2], [3], [4], [5] and has impacts on bacterial growth rate in culture. The deletion of both the synthase genes and the responder genes for both 3-oxo-N-dodecanoyl-L-homoserine lactone (3OC12HSL) and the other principal homoserine lactone QS signal produced by P. aeruginosa , N-butyryl-L-homoserine lactone (C4HSL) should result in a quadruple knockout that will not respond to or produce 3OC12HSL or C4HSL.…”

Section: Introductionmentioning

confidence: 99%

A Quadruple Knockout of lasIR and rhlIR of Pseudomonas aeruginosa PAO1 That Retains Wild-Type Twitching Motility Has Equivalent Infectivity and Persistence to PAO1 in a Mouse Model of Lung Infection

et al. 2013

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It has been widely reported that quorum-sensing incapable strains of Pseudomonas aeruginosa are less virulent than wild type strains. However, quorum sensing mutants of P. aeruginosa have been shown to develop other spontaneous mutations under prolonged culture conditions, and one of the phenotypes of P. aeruginosa that is frequently affected by this phenomenon is type IV pili-dependent motility, referred to as twitching motility. As twitching motility has been reported to be important for adhesion and colonisation, we aimed to generate a quorum-sensing knockout for which the heritage was recorded and the virulence factor production in areas unrelated to quorum sensing was known to be intact. We created a lasIRrhlIR quadruple knockout in PAO1 using a published technique that allows for the deletion of antibiotic resistance cartridges following mutagenesis, to create an unmarked QS knockout of PAO1, thereby avoiding the need for use of antibiotics in culturing, which can have subtle effects on bacterial phenotype. We phenotyped this mutant demonstrating that it produced reduced levels of protease and elastase, barely detectable levels of pyoverdin and undetectable levels of the quorum sensing signal molecules N-3-oxododecanoly-L-homoserine lactone and N-butyryl homoserine lactone, but retained full twitching motility. We then used a mouse model of acute lung infection with P. aeruginosa to demonstrate that the lasIRrhlIR knockout strain showed equal persistence to wild type parental PAO1, induced equal or greater neutrophil infiltration to the lungs, and induced similar levels of expression of inflammatory cytokines in the lungs and similar antibody responses, both in terms of magnitude and isotype. Our results suggest, in contrast to previous reports, that lack of quorum sensing alone does not significantly affect the immunogenicity, infectiveness and persistence of P. aeruginosa in a mouse model of acute lung infection.

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Section: Introductionmentioning

confidence: 99%

A Quadruple Knockout of lasIR and rhlIR of Pseudomonas aeruginosa PAO1 That Retains Wild-Type Twitching Motility Has Equivalent Infectivity and Persistence to PAO1 in a Mouse Model of Lung Infection

et al. 2013

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“…aeruginosa exports invasion determinants using theMexAB-OprM system [107]. However, the essential involvement of QSSs such as C4-HSL and 3OC12-HSL was not apparent in additional experiments, so the specific molecule involved in virulence remains unidentified [108].…”

Section: The Role Of Rnd Multidrug Efflux Pumps In P Aeruginosamentioning

confidence: 99%

“…Since the invasiveness of the mexAB-oprM -deletion mutant was restored by adding culture supernatant from MDCK cells infected with the wild-type, the authors suggested that P. aeruginosa exports invasion determinants using theMexAB-OprM system [ 107 ]. However, the essential involvement of QSSs such as C4-HSL and 3OC12-HSL was not apparent in additional experiments, so the specific molecule involved in virulence remains unidentified [ 108 ].…”

Section: The Role Of Rnd Multidrug Efflux Pumps In P Ae...mentioning

confidence: 99%

Drug resistance and physiological roles of RND multidrug efflux pumps in Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa

et al. 2023

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Drug efflux pumps transport antimicrobial agents out of bacteria, thereby reducing the intracellular antimicrobial concentration, which is associated with intrinsic and acquired bacterial resistance to these antimicrobials. As genome analysis has advanced, many drug efflux pump genes have been detected in the genomes of bacterial species. In addition to drug resistance, these pumps are involved in various essential physiological functions, such as bacterial adaptation to hostile environments, toxin and metabolite efflux, biofilm formation and quorum sensing. In Gram-negative bacteria, efflux pumps in the resistance–nodulation–division (RND) superfamily play a clinically important role. In this review, we focus on Gram-negative bacteria, including Salmonella enterica , Escherichia coli and Pseudomonas aeruginosa , and discuss the role of RND efflux pumps in drug resistance and physiological functions.

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Active Efflux Influences the Potency of Quorum Sensing Inhibitors in Pseudomonas aeruginosa

et al. 2014

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Many bacteria regulate gene expression through a cell-cell signaling process called quorum sensing (QS). In proteobacteria, QS is largely mediated by signaling molecules known as N-acylated L-homoserine lactones (AHLs) and their associated intracellular LuxR-type receptors. The design of non-native small molecules capable of inhibiting LuxR-type receptors, and thereby QS, in proteobacteria is an active area of research, and numerous lead compounds are AHL derivatives that mimic native AHL signals. Much of this past work has focused on the pathogen Pseudomonas aeruginosa, which controls an arsenal of virulence factors and biofilm formation through QS. The MexAB-OprM drug efflux pump has been shown to play a role in the secretion of the major AHL signal in P. aeruginosa, N-(3-oxododecanoyl) L-homoserine lactone. In the current study, we show that a variety of non-native AHLs and related derivatives capable of inhibiting LuxR-type receptors in P. aeruginosa display significantly higher potency in a P. aeruginosa Δ(mexAB-oprM) mutant, suggesting that MexAB-OprM also recognizes these compounds as substrates. We also demonstrate that the potency of 5,6-dimethyl-2-aminobenzimidazole, recently shown to be a QS and biofilm inhibitor in P. aeruginosa, is not affected by the presence or absence of the MexAB-OprM pump. These results have implications for the use of non-native AHLs and related derivatives as QS modulators in P. aeruginosa and other bacteria, and provide a potential design strategy for the development of new QS modulators that are resistant to active efflux.

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Quorum Sensing System Lactones Do Not Increase Invasiveness of a MexAB‐OprM Efflux Mutant but Do Play a Partial Role in Pseudomonas aeruginosa Invasion

Cited by 7 publications

References 20 publications

A Quadruple Knockout of lasIR and rhlIR of Pseudomonas aeruginosa PAO1 That Retains Wild-Type Twitching Motility Has Equivalent Infectivity and Persistence to PAO1 in a Mouse Model of Lung Infection

A Quadruple Knockout of lasIR and rhlIR of Pseudomonas aeruginosa PAO1 That Retains Wild-Type Twitching Motility Has Equivalent Infectivity and Persistence to PAO1 in a Mouse Model of Lung Infection

Drug resistance and physiological roles of RND multidrug efflux pumps in Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa

Active Efflux Influences the Potency of Quorum Sensing Inhibitors in Pseudomonas aeruginosa

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