α-Terpineol synergizes with gentamicin to rescue Caenorhabditis elegans from Pseudomonas aeruginosa infection by attenuating quorum sensing-regulated virulence

Chadha, Jatin; Ravi,; Singh, Jogender; Harjai, Kusum

doi:10.1016/j.lfs.2022.121267

Cited by 9 publications

(3 citation statements)

References 35 publications

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“…Based on Clinical and Laboratory Standards Institute (CLSI) guideline M07-A10 (CLSI 2018 ), the broth microdilution method was used to determine the Minimum Inhibitory Concentrations (MICs) of quercetin and baicalin against PAO1 (Xiao et al 2012 ). The MIC was defined as the minimum effective concentration that inhibited bacterial growth and did not cause broth to turn significantly red, as indicated by 0.02% resazurin dye (Chadha et al 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Quercetin: a promising virulence inhibitor of Pseudomonas aeruginosa LasB in vitro

Ren,

Zhu,

You

et al. 2024

Appl Microbiol Biotechnol

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With the inappropriate use of antibiotics, antibiotic resistance has emerged as a major dilemma for patients infected with Pseudomonas aeruginosa. Elastase B (LasB), a crucial extracellular virulence factor secreted by P. aeruginosa, has been identified as a key target for antivirulence therapy. Quercetin, a natural flavonoid, exhibits promising potential as an antivirulence agent. We aim to evaluate the impact of quercetin on P. aeruginosa LasB and elucidate the underlying mechanism. Molecular docking and molecular dynamics simulation revealed a rather favorable intermolecular interaction between quercetin and LasB. At the sub-MICs of ≤256 μg/ml, quercetin was found to effectively inhibit the production and activity of LasB elastase, as well as downregulate the transcription level of the lasB gene in both PAO1 and clinical strains of P. aeruginosa. Through correlation analysis, significant positive correlations were shown between the virulence gene lasB and the QS system regulatory genes lasI, lasR, rhlI, and rhlR in clinical strains of P. aeruginosa. Then, we found the lasB gene expression and LasB activity were significantly deficient in PAO1 ΔlasI and ΔlasIΔrhlI mutants. In addition, quercetin significantly downregulated the expression levels of regulated genes lasI, lasR, rhlI, rhlR, pqsA, and pqsR as well as effectively attenuated the synthesis of signaling molecules 3-oxo-C12-HSL and C4-HSL in the QS system of PAO1. Quercetin was also able to compete with the natural ligands OdDHL, BHL, and PQS for binding to the receptor proteins LasR, RhlR, and PqsR, respectively, resulting in the formation of more stabilized complexes. Taken together, quercetin exhibits enormous potential in combating LasB production and activity by disrupting the QS system of P. aeruginosa in vitro, thereby offering an alternative approach for the antivirulence therapy of P. aeruginosa infections. Key points • Quercetin diminished the content and activity of LasB elastase of P. aeruginosa. • Quercetin inhibited the QS system activity of P. aeruginosa. • Quercetin acted on LasB based on the QS system.

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Section: Methodsmentioning

confidence: 99%

Quercetin: a promising virulence inhibitor of Pseudomonas aeruginosa LasB in vitro

Ren,

Zhu,

You

et al. 2024

Appl Microbiol Biotechnol

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“…Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to investigate and visualize biofilms following exposure to drugs ( Chadha et al., 2023 ). Briefly, overnight cultures were inoculated to LB broth supplemented with PT22 (0.50 mg/mL, 0.75 mg/mL, and 1.00 mg/mL), gentamycin (4.00 μg/mL), piperacillin (4.00 μg/mL), gentamycin (4.00 μg/mL) + PT22 (0.50 mg/mL), and piperacillin (4.00 μg/mL) + PT22 (0.50 mg/mL).…”

Section: Methodsmentioning

confidence: 99%

1H-Pyrrole-2,5-dicarboxylic acid, a quorum sensing inhibitor from one endophytic fungus in Areca catechu L., acts as antibiotic accelerant against Pseudomonas aeruginosa

Liu,

Wang,

Zeng

et al. 2024

Front. Cell. Infect. Microbiol.

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Pseudomonas aeruginosa has already been stipulated as a “critical” pathogen, emphasizing the urgent need for researching and developing novel antibacterial agents due to multidrug resistance. Bacterial biofilm formation facilitates cystic fibrosis development and restricts the antibacterial potential of many current antibiotics. The capacity of P. aeruginosa to form biofilms and resist antibiotics is closely correlated with quorum sensing (QS). Bacterial QS is being contemplated as a promising target for developing novel antibacterial agents. QS inhibitors are a promising strategy for treating chronic infections. This study reported that the active compound PT22 (1H-pyrrole-2,5-dicarboxylic acid) isolated from Perenniporia tephropora FF2, one endophytic fungus from Areca catechu L., presents QS inhibitory activity against P. aeruginosa. Combined with gentamycin or piperacillin, PT22 functions as a novel antibiotic accelerant against P. aeruginosa. PT22 (0.50 mg/mL, 0.75 mg/mL, and 1.00 mg/mL) reduces the production of QS-related virulence factors, such as pyocyanin and rhamnolipid, and inhibits biofilm formation of P. aeruginosa PAO1 instead of affecting its growth. The architectural disruption of the biofilms was confirmed by visualization through scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Real-time quantitative PCR (RT-qPCR) indicated that PT22 significantly attenuated the expression of QS-related genes followed by docking analysis of molecules against QS activator proteins. PT22 dramatically increased the survival rate of Galleria mellonella. PT22 combined with gentamycin or piperacillin presents significant inhibition of biofilm formation and eradication of mature biofilm compared to monotherapy, which was also confirmed by visualization through SEM and CLSM. After being treated with PT22 combined with gentamycin or piperacillin, the survival rates of G. mellonella were significantly increased compared to those of monotherapy. PT22 significantly enhanced the susceptibility of gentamycin and piperacillin against P. aeruginosa PAO1. Our results suggest that PT22 from P. tephropora FF2 as a potent QS inhibitor is a candidate antibiotic accelerant to combat the antibiotic resistance of P. aeruginosa.

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“…The ability of GO-AgNP-impregnated urinary catheters to avert cellular adhesion and biofilm formation by C. auris and P. aeruginosa was assessed using field emission scanning electron microscopy [34]. Precisely, GO-AgNP-treated and -untreated catheter segments were placed in 12 well plates seeded with overnight grown cultures of C. auris and P. aeruginosa for 48 h at 37 • C. Post-incubation, the catheters were washed thrice with PBS to remove unbound cells, followed by fixation with 4% formaldehyde at room temperature for 1 h. The biofilms were then dehydrated using a gradient of ethanol in the following order: 30%, 50%, 70%, 90%, and 100% (30 min each).…”

Section: Field Emission Scanning Electron Microscopy Of Microbial Bio...mentioning

confidence: 99%

Antimicrobial and Antibiofilm Potential of Green-Synthesized Graphene–Silver Nanocomposite against Multidrug-Resistant Nosocomial Pathogens

Negi,

Chadha,

Harjai

et al. 2024

Biomedicines

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Hospital-acquired infections (HAIs) pose a significant risk to global health, impacting millions of individuals globally. These infections have increased rates of morbidity and mortality due to the prevalence of widespread antimicrobial resistance (AMR). Graphene-based nanoparticles (GBNs) are known to possess extensive antimicrobial properties by inflicting damage to the cell membrane, suppressing virulence, and inhibiting microbial biofilms. Developing alternative therapies for HAIs and addressing AMR can be made easier and more affordable by combining nanoparticles with medicinal plants harboring antimicrobial properties. Hence, this study was undertaken to develop a novel graphene–silver nanocomposite via green synthesis using Trillium govanianum plant extract as a reducing agent. The resulting nanocomposite comprised silver nanoparticles embedded in graphene sheets. The antibacterial and antifungal properties of graphene–silver nanocomposites were investigated against several nosocomial pathogens, namely, Candida auris, Candida glabrata, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The nanocomposite displayed broad-range antimicrobial potential against the test pathogens, with minimum inhibitory concentrations (MICs) ranging between 31.25 and 125.0 µg/mL, and biofilm inhibition up to 80–96%. Moreover, nanocomposite-functionalized urinary catheters demonstrated hemocompatibility towards sheep erythrocytes and imparted anti-fouling activity to the biomaterial, while also displaying biocompatibility towards HEK 293 cells. Collectively, this investigation highlights the possible application of green-synthesized GBNs as an effective alternative to conventional antibiotics for combating multidrug-resistant pathogens.

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α-Terpineol synergizes with gentamicin to rescue Caenorhabditis elegans from Pseudomonas aeruginosa infection by attenuating quorum sensing-regulated virulence

Cited by 9 publications

References 35 publications

Quercetin: a promising virulence inhibitor of Pseudomonas aeruginosa LasB in vitro

Quercetin: a promising virulence inhibitor of Pseudomonas aeruginosa LasB in vitro

1H-Pyrrole-2,5-dicarboxylic acid, a quorum sensing inhibitor from one endophytic fungus in Areca catechu L., acts as antibiotic accelerant against Pseudomonas aeruginosa

Antimicrobial and Antibiofilm Potential of Green-Synthesized Graphene–Silver Nanocomposite against Multidrug-Resistant Nosocomial Pathogens

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