Pseudomonas aeruginosa quorum sensing inhibition by clinical isolate Delftia tsuruhatensis 11304: involvement of N-octadecanoylhomoserine lactones

Malešević, Milka; Lorenzo, Flaviana Di; Filipić, Brankica; Stanisavljević, Nemanja; Novović, Katarina; Šenerović, Lidija; Polović, Natalija; Molinaro, Antonio; Kojić, Milan; Jovčić, Branko

doi:10.1038/s41598-019-52955-3

Cited by 50 publications

(26 citation statements)

References 65 publications

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“…The QS system regulates cell-to-cell communication through the interaction of QS signal molecules (N-acyl-L-homoserine lactones) with transcriptional regulators, which induces the expression of target genes. P. aeruginosa has three major and well-characterized QS systems: las, rhl, and the Pseudomonas quinolone signal (PQS) [ 138 ]. The Las system is composed of a transcriptional regulator LasR and the signal molecule N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C 12 HSL), synthesized by the enzyme LasI.…”

Section: Oxidative Stress Responses In P Aeruginosamentioning

confidence: 99%

Oxidative Stress Response in Pseudomonas aeruginosa

et al. 2021

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Pseudomonas aeruginosa is a Gram-negative environmental and human opportunistic pathogen highly adapted to many different environmental conditions. It can cause a wide range of serious infections, including wounds, lungs, the urinary tract, and systemic infections. The high versatility and pathogenicity of this bacterium is attributed to its genomic complexity, the expression of several virulence factors, and its intrinsic resistance to various antimicrobials. However, to thrive and establish infection, P. aeruginosa must overcome several barriers. One of these barriers is the presence of oxidizing agents (e.g., hydrogen peroxide, superoxide, and hypochlorous acid) produced by the host immune system or that are commonly used as disinfectants in a variety of different environments including hospitals. These agents damage several cellular molecules and can cause cell death. Therefore, bacteria adapt to these harsh conditions by altering gene expression and eliciting several stress responses to survive under oxidative stress. Here, we used PubMed to evaluate the current knowledge on the oxidative stress responses adopted by P. aeruginosa. We will describe the genes that are often differently expressed under oxidative stress conditions, the pathways and proteins employed to sense and respond to oxidative stress, and how these changes in gene expression influence pathogenicity and the virulence of P. aeruginosa. Understanding these responses and changes in gene expression is critical to controlling bacterial pathogenicity and developing new therapeutic agents.

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Section: Oxidative Stress Responses In P Aeruginosamentioning

confidence: 99%

Oxidative Stress Response in Pseudomonas aeruginosa

et al. 2021

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“…Pathogenic bacteria such as Pseudomonas aeruginosa regulate their pathogenicity, virulence factor production, and biofilm formation via QS. 8 P. aeruginosa is an infectious opportunistic bacteria, primarily causing nosocomial infections, which leads to mortality in immune-compromised patients. 9 In P. aeruginosa , N -acyl homoserine lactones (AHLs) activate the QS signaling, which is regulated by three frameworks: las, rhl, and pqs systems 10 that are interlinked by intracellular signaling molecules (autoinducers) and Pseudomonas quinolone-based signal (PQS), provided by the bacterial cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-quorum Sensing and Anti-biofilm Activity of Zinc Oxide Nanospikes

et al. 2020

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This study evaluates the impact of two separate incubation periods (4 and 6 weeks) on the morphology of sol–gel-fabricated ZnO nanospikes (ZNs), that is, ZN1 and ZN2, respectively. We further analyzed the inhibitory effects of ZN1 and ZN2 on quorum sensing (QS) and biofilm formation in Pseudomonas aeruginosa (PAO1) and Chromobacterium violaceum (strains 12472 and CVO26). The size of the synthesized ZNs was in the range of 40–130 nm, and finer nanoparticles were synthesized after an incubation period of 6 weeks. Treatment with ZNs decreased the production of violacein in the pathogen without affecting the bacterial growth, which indicated that ZNs inhibited the QS signaling regulated by N -acyl homoserine lactone. ZN2 had a higher inhibitory action on the virulence factor productivity than ZN1. Furthermore, ZN2-treated cells displayed a substantial decrease in azocasein-degrading protease activity (80%), elastase activity (83%), and pyocyanin production (85%) relative to untreated P. aeruginosa PAO1 cells. Treatment with ZN2 decreased swarming motility and exopolysaccharide production by 89 and 85%, respectively. ZN2 was effective against both the las & pqs systems of P. aeruginosa and exhibited broad-spectrum activity. Additionally, ZN2 was more efficient in inhibiting the biofilm formation at the attachment stage than ZN1. These findings revealed that in P. aeruginosa , ZN2 demonstrated inhibitory effects on QS as well as on the development of biofilms. Thus, ZN2 can be potentially used to treat drug-resistant P. aeruginosa infections.

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“…Much effort has been put into the inhibition of pigmented virulence factors such as staphyloxanthin and pyocyanin 71,72 but the approach is taken to their modulation is rather distinct. The first relies on the inhibition of druggable targets that are responsible for staphyloxanthin biosynthesis, 73,74 whereas the second is focussed on the modulation of quorum sensing mechanisms that lie upstream the biosynthetic pathway that builds up this virulence factor [75][76][77][78] . [83].…”

Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of thiazolidinedione derivatives with high ligand efficiency to P. aeruginosa PhzS

Froes

Chaves

Mendes

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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The thiazolidinone ring is found in compounds that have widespan biology activity and there is mechanism-based evidence that compounds bearing this moiety inhibit P. aeruginosa PhzS (PaPzhS), a key enzyme in the biosynthesis of the virulence factor named pyocyanin. Ten novel thiazolidinone derivatives were synthesised and screened against PaPhzS, using two orthogonal assays. The biological results provided by these and 28 other compounds, whose synthesis had been described, suggest that the dihydroquinazoline ring, found in the previous hit (A-Kd ¼ 18 mM and LE ¼ 0.20), is not required for PaPzhS inhibition, but unsubstituted nitrogen at the thiazolidinone ring is. The molecular simplification approach, pursued in this work, afforded an optimised lead compound (13-5-(2,4-dimethoxyphenyl)thiazolidine-2,4dione) with 10-fold improvement in affinity (Kd¼ 1.68 mM) and more than 100% increase in LE (0.45), which follows the same inhibition mode as the original hit compound (competitive to NADH).

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Pseudomonas aeruginosa quorum sensing inhibition by clinical isolate Delftia tsuruhatensis 11304: involvement of N-octadecanoylhomoserine lactones

Cited by 50 publications

References 65 publications

Oxidative Stress Response in Pseudomonas aeruginosa

Oxidative Stress Response in Pseudomonas aeruginosa

Anti-quorum Sensing and Anti-biofilm Activity of Zinc Oxide Nanospikes

Synthesis and biological evaluation of thiazolidinedione derivatives with high ligand efficiency to P. aeruginosa PhzS

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